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INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,670,797
pmid-10807004|pmid-1962210|pmid-12691534|pmid-15025524|pmid-17226957
Figure 1.Structures of PMO and (RX)8− PMO conjugate.
[ "1", "2", "3", "4" ]
52
8,200
0
false
Figure 1.Structures of PMO and (RX)8− PMO conjugate.
[]
Figure 1.Structures of PMO and (RX)8− PMO conjugate.
true
true
true
true
true
1,326
1
INTRODUCTION
0
null
null
17,670,797
pmid-17097177|pmid-17097177
Structures of PMO and (RX)8− PMO conjugate.
null
43
8,201
0
false
null
null
Structures of PMO and (RX)8− PMO conjugate.
true
true
true
true
true
1,327
2
INTRODUCTION
1
5
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
Important considerations in the design of effective CPPs include the ability to deliver AO efficiently, stability in living systems and toxicity.
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
145
8,202
0
false
Important considerations in the design of effective CPPs include the ability to deliver AO efficiently, stability in living systems and toxicity.
[]
Important considerations in the design of effective CPPs include the ability to deliver AO efficiently, stability in living systems and toxicity.
true
true
true
true
true
1,328
2
INTRODUCTION
1
5
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
We have reported that Tat and oligoarginine peptides are not stable in human serum (5), and are therefore ill-suited for in vivo applications.
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
142
8,203
1
false
We have reported that Tat and oligoarginine peptides are not stable in human serum, and are therefore ill-suited for in vivo applications.
[ "5" ]
We have reported that Tat and oligoarginine peptides are not stable in human serum, and are therefore ill-suited for in vivo applications.
true
true
true
true
true
1,328
2
INTRODUCTION
1
5
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
Oligoarginine peptides incorporating non-α amino acids have been proven superior to oligoarginine alone.
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
104
8,204
0
false
Oligoarginine peptides incorporating non-α amino acids have been proven superior to oligoarginine alone.
[]
Oligoarginine peptides incorporating non-α amino acids have been proven superior to oligoarginine alone.
true
true
true
true
true
1,328
2
INTRODUCTION
1
5
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
CPPs containing 6-aminohexanoic acid (X) and β-alanine (B) were more stable in human serum than Tat or oligoarginine peptides (5).
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
130
8,205
1
false
CPPs containing 6-aminohexanoic acid (X) and β-alanine (B) were more stable in human serum than Tat or oligoarginine peptides.
[ "5" ]
CPPs containing 6-aminohexanoic acid (X) and β-alanine (B) were more stable in human serum than Tat or oligoarginine peptides.
true
true
true
true
true
1,328
2
INTRODUCTION
1
6
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
A CPP−PMO conjugate, (RXR)4−PMO, has been shown to be more efficient in the correction of pre-mRNA mis-splicing (6) and in inhibition of the replication of mouse hepatitis virus in vivo (7) than an oligoarginine peptide.
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
220
8,206
1
false
A CPP−PMO conjugate, (RXR)4−PMO, has been shown to be more efficient in the correction of pre-mRNA mis-splicing and in inhibition of the replication of mouse hepatitis virus in vivo than an oligoarginine peptide.
[ "6", "7" ]
A CPP−PMO conjugate, (RXR)4−PMO, has been shown to be more efficient in the correction of pre-mRNA mis-splicing and in inhibition of the replication of mouse hepatitis virus in vivo than an oligoarginine peptide.
true
true
true
true
true
1,328
2
INTRODUCTION
1
8
[ "B5", "B5", "B6", "B7", "B8", "B9", "B7", "B11 B12 B13", "B7", "B13" ]
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
In addition, (RXR)4−PMO conjugates have been shown to cause effective exon skipping in muscle cells from DMD dogs (8), in human muscle explants (9) and in mdx mice (10), as well as inhibiting the replication of various viruses in cell cultures (7,11–13) and in mice (7,13).
[ "5", "5", "6", "7", "8", "9", "7", "11–13", "7", "13" ]
273
8,207
1
false
In addition, (RXR)4−PMO conjugates have been shown to cause effective exon skipping in muscle cells from DMD dogs, in human muscle explants and in mdx mice (10), as well as inhibiting the replication of various viruses in cell cultures and in mice.
[ "8", "9", "7,11–13", "7,13" ]
In addition, (RXR)4−PMO conjugates have been shown to cause effective exon skipping in muscle cells from DMD dogs, in human muscle explants and in mdx mice (10), as well as inhibiting the replication of various viruses in cell cultures and in mice.
true
true
true
true
true
1,328
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
The above studies have helped make it clear that unnatural amino acids can confer enhanced stability and activity, and therefore improve the potential of CPPs to deliver therapeutic PMO.
[ "5", "13" ]
186
8,208
0
false
The above studies have helped make it clear that unnatural amino acids can confer enhanced stability and activity, and therefore improve the potential of CPPs to deliver therapeutic PMO.
[]
The above studies have helped make it clear that unnatural amino acids can confer enhanced stability and activity, and therefore improve the potential of CPPs to deliver therapeutic PMO.
true
true
true
true
true
1,329
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
In pursuit of CPPs with improved characteristics, we have carried out a structure–activity relationship study to investigate the effects of unnatural amino acid insertions in oligoarginine peptides on cellular delivery, nuclear antisense activity, toxicity and serum-binding characteristics of the resulting CPP−PMO conj...
[ "5", "13" ]
327
8,209
0
false
In pursuit of CPPs with improved characteristics, we have carried out a structure–activity relationship study to investigate the effects of unnatural amino acid insertions in oligoarginine peptides on cellular delivery, nuclear antisense activity, toxicity and serum-binding characteristics of the resulting CPP−PMO conj...
[]
In pursuit of CPPs with improved characteristics, we have carried out a structure–activity relationship study to investigate the effects of unnatural amino acid insertions in oligoarginine peptides on cellular delivery, nuclear antisense activity, toxicity and serum-binding characteristics of the resulting CPP−PMO conj...
true
true
true
true
true
1,329
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
The unnatural amino acids studied here are X, B and D-arginine (r).
[ "5", "13" ]
67
8,210
0
false
The unnatural amino acids studied here are X, B and D-arginine (r).
[]
The unnatural amino acids studied here are X, B and D-arginine (r).
true
true
true
true
true
1,329
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
We chose to study the X amino acid based on the successes of the (RXR)4 CPP in several studies as shown in the previous paragraph.
[ "5", "13" ]
130
8,211
0
false
We chose to study the X amino acid based on the successes of the (RXR)4 CPP in several studies as shown in the previous paragraph.
[]
We chose to study the X amino acid based on the successes of the (RXR)4 CPP in several studies as shown in the previous paragraph.
true
true
true
true
true
1,329
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
B and r amino acids were chosen because they have good enzymatic stability (5).
[ "5", "13" ]
79
8,212
1
false
B and r amino acids were chosen because they have good enzymatic stability.
[ "5" ]
B and r amino acids were chosen because they have good enzymatic stability.
true
true
true
true
true
1,329
3
INTRODUCTION
1
5
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
The CPPs are (i) the oligoarginine sequences, R8 and R9, (ii) sequences with RXR, RX and RB repeats, as well as various combinations thereof, and (iii) sequences containing D-arginine, r8, (rX)8 (rXR)4, (rXr)4 and (rB)8.
[ "5", "13" ]
220
8,213
0
false
The CPPs are (i) the oligoarginine sequences, R8 and R9, (ii) sequences with RXR, RX and RB repeats, as well as various combinations thereof, and (iii) sequences containing D-arginine, r8, (rX)8 (rXR)4, (rXr)4 and (rB)8.
[]
The CPPs are (i) the oligoarginine sequences, R8 and R9, (ii) sequences with RXR, RX and RB repeats, as well as various combinations thereof, and (iii) sequences containing D-arginine, r8, (rX)8 (rXR)4, (rXr)4 and (rB)8.
true
true
true
true
true
1,329
3
INTRODUCTION
1
13
[ "B5", "B13" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
The CPP−PMO conjugates were evaluated for their relative (a) cellular uptake, as determined by flow cytometry, (b) antisense activity, as determined by a splice correction assay (13) and (c) cellular toxicity, as determined by MTT cell viability, propidium iodide membrane integrity and hemolysis assays, as well as by m...
[ "5", "13" ]
339
8,214
1
false
The CPP−PMO conjugates were evaluated for their relative (a) cellular uptake, as determined by flow cytometry, (b) antisense activity, as determined by a splice correction assay and (c) cellular toxicity, as determined by MTT cell viability, propidium iodide membrane integrity and hemolysis assays, as well as by micros...
[ "13" ]
The CPP−PMO conjugates were evaluated for their relative (a) cellular uptake, as determined by flow cytometry, (b) antisense activity, as determined by a splice correction assay and (c) cellular toxicity, as determined by MTT cell viability, propidium iodide membrane integrity and hemolysis assays, as well as by micros...
true
true
true
true
true
1,329
0
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-10807004|pmid-1962210|pmid-12691534|pmid-15025524|pmid-17226957
The naturally occurring CPPs such as Tat peptide are not stable in blood and neither are oligolysine/oligoarginine (5), rendering these CPPs unfavorable as transporters for therapeutic AOs.
[ "5" ]
189
8,215
1
false
The naturally occurring CPPs such as Tat peptide are not stable in blood and neither are oligolysine/oligoarginine, rendering these CPPs unfavorable as transporters for therapeutic AOs.
[ "5" ]
The naturally occurring CPPs such as Tat peptide are not stable in blood and neither are oligolysine/oligoarginine, rendering these CPPs unfavorable as transporters for therapeutic AOs.
true
true
true
true
true
1,330
0
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-10807004|pmid-1962210|pmid-12691534|pmid-15025524|pmid-17226957
We reasoned that one approach to improve stability would be to use non-α amino acids or D-amino acids.
[ "5" ]
102
8,216
0
false
We reasoned that one approach to improve stability would be to use non-α amino acids or D-amino acids.
[]
We reasoned that one approach to improve stability would be to use non-α amino acids or D-amino acids.
true
true
true
true
true
1,330
0
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-10807004|pmid-1962210|pmid-12691534|pmid-15025524|pmid-17226957
In this study, we investigated whether incorporation of 6-aminohexanoic acid (X), β-alanine (B) and D-arginine (r) amino acids into the CPP would affect cellular delivery, antisense activity, toxicity and serum binding of the resulting CPP−PMO conjugates.
[ "5" ]
255
8,217
0
false
In this study, we investigated whether incorporation of 6-aminohexanoic acid (X), β-alanine (B) and D-arginine (r) amino acids into the CPP would affect cellular delivery, antisense activity, toxicity and serum binding of the resulting CPP−PMO conjugates.
[]
In this study, we investigated whether incorporation of 6-aminohexanoic acid (X), β-alanine (B) and D-arginine (r) amino acids into the CPP would affect cellular delivery, antisense activity, toxicity and serum binding of the resulting CPP−PMO conjugates.
true
true
true
true
true
1,330
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
We found that CPP−PMOF conjugates containing X/B residues did not enter cells as efficiently as R8− and R9−PMO conjugates.
[ "6", "6" ]
122
8,218
0
false
We found that CPP−PMOF conjugates containing X/B residues did not enter cells as efficiently as R8− and R9−PMO conjugates.
[]
We found that CPP−PMOF conjugates containing X/B residues did not enter cells as efficiently as R8− and R9−PMO conjugates.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
This is consistent with our previous finding for the (RXR)4 conjugate (6).
[ "6", "6" ]
74
8,219
1
false
This is consistent with our previous finding for the (RXR)4 conjugate.
[ "6" ]
This is consistent with our previous finding for the (RXR)4 conjugate.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
We have found that cell surface proteoglycans were involved with binding of the Tat−, R9F2− and (RXR)4−PMO conjugates with the (RXR)4 conjugate having the lowest binding affinity.
[ "6", "6" ]
179
8,220
0
false
We have found that cell surface proteoglycans were involved with binding of the Tat−, R9F2− and (RXR)4−PMO conjugates with the (RXR)4 conjugate having the lowest binding affinity.
[]
We have found that cell surface proteoglycans were involved with binding of the Tat−, R9F2− and (RXR)4−PMO conjugates with the (RXR)4 conjugate having the lowest binding affinity.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
Insertion of X into an oligoarginine CPP reduces the charge density and may lead to decreased binding affinity for proteoglycans.
[ "6", "6" ]
129
8,221
0
false
Insertion of X into an oligoarginine CPP reduces the charge density and may lead to decreased binding affinity for proteoglycans.
[]
Insertion of X into an oligoarginine CPP reduces the charge density and may lead to decreased binding affinity for proteoglycans.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
Despite the lower cellular uptake of X/B-containing CPP–PMO, they generated higher antisense activities in the cell nucleus than oligoarginine−PMO.
[ "6", "6" ]
147
8,222
0
false
Despite the lower cellular uptake of X/B-containing CPP–PMO, they generated higher antisense activities in the cell nucleus than oligoarginine−PMO.
[]
Despite the lower cellular uptake of X/B-containing CPP–PMO, they generated higher antisense activities in the cell nucleus than oligoarginine−PMO.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
We have found that endocytosis was the internalization mechanism (at least primarily) for oligoarginine- and (RXR)4−PMO conjugates.
[ "6", "6" ]
131
8,223
0
false
We have found that endocytosis was the internalization mechanism (at least primarily) for oligoarginine- and (RXR)4−PMO conjugates.
[]
We have found that endocytosis was the internalization mechanism (at least primarily) for oligoarginine- and (RXR)4−PMO conjugates.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
Indication of different uptake mechanisms was not found among these conjugates (6).
[ "6", "6" ]
83
8,224
1
false
Indication of different uptake mechanisms was not found among these conjugates.
[ "6" ]
Indication of different uptake mechanisms was not found among these conjugates.
true
true
true
true
true
1,331
1
DISCUSSION
1
6
[ "B6", "B6" ]
17,670,797
pmid-17097177|pmid-17097177
Therefore we hypothesize that X/B-containing conjugates have a greater ability to escape from endosomes/lysosomes than oligoarginine conjugates by a mechanism as yet to be studied.
[ "6", "6" ]
180
8,225
0
false
Therefore we hypothesize that X/B-containing conjugates have a greater ability to escape from endosomes/lysosomes than oligoarginine conjugates by a mechanism as yet to be studied.
[]
Therefore we hypothesize that X/B-containing conjugates have a greater ability to escape from endosomes/lysosomes than oligoarginine conjugates by a mechanism as yet to be studied.
true
true
true
true
true
1,331
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
The number of X residues affects both the nuclear antisense activity and the toxicity of conjugates.
null
100
8,226
0
false
null
null
The number of X residues affects both the nuclear antisense activity and the toxicity of conjugates.
true
true
true
true
true
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
The CPP−PMO conjugate with 8 X residues [(RX)8−PMO] had the highest activity followed by one with 5 Xs
null
102
8,227
0
false
null
null
The CPP−PMO conjugate with 8 X residues [(RX)8−PMO] had the highest activity followed by one with 5 Xs
true
true
false
true
false
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
[(RXR)4−PMO] (Figures 1 and 4).
null
31
8,228
0
false
null
null
[(RXR)4−PMO] (Figures 1 and 4).
false
false
true
true
false
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
However, these conjugates were toxic to cells at higher concentrations, which may be a concern when considering potential applications for in vivo delivery of PMO.
null
163
8,229
0
false
null
null
However, these conjugates were toxic to cells at higher concentrations, which may be a concern when considering potential applications for in vivo delivery of PMO.
true
true
true
true
true
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
Replacement of all 8 Xs with Bs decreased both toxicity and antisense activity.
null
79
8,230
0
false
null
null
Replacement of all 8 Xs with Bs decreased both toxicity and antisense activity.
true
true
true
true
true
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
The combination of 3–4 Xs with several B residues yielded CPPs with no detectable toxicity, and at some concentrations several of them had similar antisense activity as (RX)8−PMO.
null
179
8,231
0
false
null
null
The combination of 3–4 Xs with several B residues yielded CPPs with no detectable toxicity, and at some concentrations several of them had similar antisense activity as (RX)8−PMO.
true
true
true
true
true
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
We think this type of CPP, having Bs and fewer than 5 Xs, will offer balanced activity and low toxicity as well as the stability, and have considerable potential for delivery of therapeutic AOs.
null
194
8,232
0
false
null
null
We think this type of CPP, having Bs and fewer than 5 Xs, will offer balanced activity and low toxicity as well as the stability, and have considerable potential for delivery of therapeutic AOs.
true
true
true
true
true
1,332
2
DISCUSSION
0
null
null
17,670,797
pmid-17226957|pmid-17226957|pmid-17097177|pmid-17344287|pmid-16724091|pmid-16919955|pmid-17344287|pmid-15795246|pmid-16966399|pmid-16987987|pmid-17344287|pmid-16987987
Further investigation into the toxicity and activity versus dosing levels of these CPPs in vivo is warranted.
null
109
8,233
0
false
null
null
Further investigation into the toxicity and activity versus dosing levels of these CPPs in vivo is warranted.
true
true
true
true
true
1,332
3
DISCUSSION
1
20
[ "B19", "B20" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
Surprisingly, the replacement of L-arginine with D-arginine enhanced neither uptake nor antisense activity for oligoarginine, or X- and B-containing conjugates.
[ "20", "21" ]
160
8,234
0
false
Surprisingly, the replacement of L-arginine with D-arginine enhanced neither uptake nor antisense activity for oligoarginine, or X- and B-containing conjugates.
[]
Surprisingly, the replacement of L-arginine with D-arginine enhanced neither uptake nor antisense activity for oligoarginine, or X- and B-containing conjugates.
true
true
true
true
true
1,333
3
DISCUSSION
1
20
[ "B19", "B20" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
In the case of (RX)8−PMO, the replacement actually caused a small but statistically significant decrease in activity.
[ "20", "21" ]
117
8,235
0
false
In the case of (RX)8−PMO, the replacement actually caused a small but statistically significant decrease in activity.
[]
In the case of (RX)8−PMO, the replacement actually caused a small but statistically significant decrease in activity.
true
true
true
true
true
1,333
3
DISCUSSION
1
20
[ "B19", "B20" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
Our observation is different from the results reported by others (20,21) who found that D-CPPs had higher cellular uptake than L-CPPs, although no biological functional cargo was used in their study.
[ "20", "21" ]
199
8,236
0
false
Our observation is different from the results reported by others who found that D-CPPs had higher cellular uptake than L-CPPs, although no biological functional cargo was used in their study.
[ "20,21" ]
Our observation is different from the results reported by others who found that D-CPPs had higher cellular uptake than L-CPPs, although no biological functional cargo was used in their study.
true
true
true
true
true
1,333
3
DISCUSSION
1
20
[ "B19", "B20" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
The difference between results may be due to the type and size of cargos and the cell lines used for the assays.
[ "20", "21" ]
112
8,237
0
false
The difference between results may be due to the type and size of cargos and the cell lines used for the assays.
[]
The difference between results may be due to the type and size of cargos and the cell lines used for the assays.
true
true
true
true
true
1,333
3
DISCUSSION
1
20
[ "B19", "B20" ]
17,670,797
pmid-17226957|pmid-16987987|pmid-12411431|pmid-12166934
Whether the use of D-arginine-containing peptides results in superior CPP−PMO functional activity in vivo remains to be tested.
[ "20", "21" ]
127
8,238
0
false
Whether the use of D-arginine-containing peptides results in superior CPP−PMO functional activity in vivo remains to be tested.
[]
Whether the use of D-arginine-containing peptides results in superior CPP−PMO functional activity in vivo remains to be tested.
true
true
true
true
true
1,333
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
We attempted to understand the nature of (RX)8− and (RXR)4−PMO toxicity.
[ "5", "5" ]
72
8,239
0
false
We attempted to understand the nature of (RX)8− and (RXR)4−PMO toxicity.
[]
We attempted to understand the nature of (RX)8− and (RXR)4−PMO toxicity.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
It is apparent that these two conjugates caused little immediate membrane damage with 0.5 or 5 h treatment at concentrations as high as 60 μM (Figure 8).
[ "5", "5" ]
153
8,240
0
false
It is apparent that these two conjugates caused little immediate membrane damage with 0.5 or 5 h treatment at concentrations as high as 60 μM (Figure 8).
[]
It is apparent that these two conjugates caused little immediate membrane damage with 0.5 or 5 h treatment at concentrations as high as 60 μM (Figure 8).
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
However, these two conjugates had dose-dependent toxicity with 24 hr treatment as shown by the leaky cell membranes and fewer cells compared to controls (Figure 6C&D, Figure 8).
[ "5", "5" ]
177
8,241
0
false
However, these two conjugates had dose-dependent toxicity with 24 hr treatment as shown by the leaky cell membranes and fewer cells compared to controls (Figure 6C&D, Figure 8).
[]
However, these two conjugates had dose-dependent toxicity with 24 hr treatment as shown by the leaky cell membranes and fewer cells compared to controls (Figure 6C&D, Figure 8).
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
Interestingly, the replacement of Xs with Bs in (RX)8−PMO abolished the toxicity, and the replacement of L-arginine with D-arginine reduced the toxicity of (RX)8−PMO (Figure 6).
[ "5", "5" ]
177
8,242
0
false
Interestingly, the replacement of Xs with Bs in (RX)8−PMO abolished the toxicity, and the replacement of L-arginine with D-arginine reduced the toxicity of (RX)8−PMO (Figure 6).
[]
Interestingly, the replacement of Xs with Bs in (RX)8−PMO abolished the toxicity, and the replacement of L-arginine with D-arginine reduced the toxicity of (RX)8−PMO (Figure 6).
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
We have found that (rX)8−PMO was completely stable and the peptide portion of (RB)8−PMO was only partially degraded, whereas the peptide portion of (RX)8−PMO was completely degraded in cells (5).
[ "5", "5" ]
195
8,243
1
false
We have found that (rX)8−PMO was completely stable and the peptide portion of (RB)8−PMO was only partially degraded, whereas the peptide portion of (RX)8−PMO was completely degraded in cells.
[ "5" ]
We have found that (rX)8−PMO was completely stable and the peptide portion of (RB)8−PMO was only partially degraded, whereas the peptide portion of (RX)8−PMO was completely degraded in cells.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
We wondered whether the difference in toxicity among (RX)8, (RB)8 and (rX)8−PMO conjugates was caused by differences in intracellular stability, resulting in the metabolized products of (RX)8−PMO producing toxicity.
[ "5", "5" ]
215
8,244
0
false
We wondered whether the difference in toxicity among (RX)8, (RB)8 and (rX)8−PMO conjugates was caused by differences in intracellular stability, resulting in the metabolized products of (RX)8−PMO producing toxicity.
[]
We wondered whether the difference in toxicity among (RX)8, (RB)8 and (rX)8−PMO conjugates was caused by differences in intracellular stability, resulting in the metabolized products of (RX)8−PMO producing toxicity.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
The identifiable metabolized products of (RX)8−PMO were XRXB−PMO and XB−PMO (5) but neither product had any detectable toxicity as measured by MTT assay (data not shown).
[ "5", "5" ]
170
8,245
1
false
The identifiable metabolized products of (RX)8−PMO were XRXB−PMO and XB−PMO but neither product had any detectable toxicity as measured by MTT assay (data not shown).
[ "5" ]
The identifiable metabolized products of (RX)8−PMO were XRXB−PMO and XB−PMO but neither product had any detectable toxicity as measured by MTT assay (data not shown).
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
It is possible that the CPP portion was degraded into free amino acids and/or smaller peptide fragments which were toxic.
[ "5", "5" ]
121
8,246
0
false
It is possible that the CPP portion was degraded into free amino acids and/or smaller peptide fragments which were toxic.
[]
It is possible that the CPP portion was degraded into free amino acids and/or smaller peptide fragments which were toxic.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
However, our investigation revealed that neither free R nor X, alone or in combination, caused cellular toxicity.
[ "5", "5" ]
113
8,247
0
false
However, our investigation revealed that neither free R nor X, alone or in combination, caused cellular toxicity.
[]
However, our investigation revealed that neither free R nor X, alone or in combination, caused cellular toxicity.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
Another possibility is that because of the high hydrophobicity of X compared to B, X in combination with positively charged arginine residues leads to toxicity not generated by B residue combinations.
[ "5", "5" ]
200
8,248
0
false
Another possibility is that because of the high hydrophobicity of X compared to B, X in combination with positively charged arginine residues leads to toxicity not generated by B residue combinations.
[]
Another possibility is that because of the high hydrophobicity of X compared to B, X in combination with positively charged arginine residues leads to toxicity not generated by B residue combinations.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
However, this explanation does not account for the difference in toxicity observed between (RX)8−PMO and (rX)8−PMO, which have the same hydrophobicity.
[ "5", "5" ]
151
8,249
0
false
However, this explanation does not account for the difference in toxicity observed between (RX)8−PMO and (rX)8−PMO, which have the same hydrophobicity.
[]
However, this explanation does not account for the difference in toxicity observed between (RX)8−PMO and (rX)8−PMO, which have the same hydrophobicity.
true
true
true
true
true
1,334
4
DISCUSSION
1
5
[ "B5", "B5" ]
17,670,797
pmid-17226957|pmid-17226957
Perhaps the toxicity of (RXR)4−PMO and (RX)8−PMO was caused by the peptide fragments that we could not identify by mass spectrometry.
[ "5", "5" ]
133
8,250
0
false
Perhaps the toxicity of (RXR)4−PMO and (RX)8−PMO was caused by the peptide fragments that we could not identify by mass spectrometry.
[]
Perhaps the toxicity of (RXR)4−PMO and (RX)8−PMO was caused by the peptide fragments that we could not identify by mass spectrometry.
true
true
true
true
true
1,334
5
DISCUSSION
0
null
null
17,670,797
null
Unlike the toxicity difference between (RX)8− and (rX)8−PMO, the L→D replacement did not change the toxicity of (RXR)4−PMO (Figure 6).
null
134
8,251
0
false
null
null
Unlike the toxicity difference between (RX)8− and (rX)8−PMO, the L→D replacement did not change the toxicity of (RXR)4−PMO (Figure 6).
true
true
true
true
true
1,335
5
DISCUSSION
0
null
null
17,670,797
null
Substitution of either one R (rXR) or two R (rXr) from the RXR repeat neither reduced nor increased the toxicity profile of (RXR)4−PMO.
null
135
8,252
0
false
null
null
Substitution of either one R (rXR) or two R (rXr) from the RXR repeat neither reduced nor increased the toxicity profile of (RXR)4−PMO.
true
true
true
true
true
1,335
5
DISCUSSION
0
null
null
17,670,797
null
At this point, we do not fully understand the mechanisms of (RXR)4− and (RX)8−PMO conjugate toxicity, but look forward to studying this topic further.
null
150
8,253
0
false
null
null
At this point, we do not fully understand the mechanisms of (RXR)4− and (RX)8−PMO conjugate toxicity, but look forward to studying this topic further.
true
true
true
true
true
1,335
6
DISCUSSION
0
null
null
17,670,797
null
Serum effect on the activity of a CPP−AO conjugates is an important issue when considering potential in vivo applications.
null
122
8,254
0
false
null
null
Serum effect on the activity of a CPP−AO conjugates is an important issue when considering potential in vivo applications.
true
true
true
true
true
1,336
6
DISCUSSION
0
null
null
17,670,797
null
X/B-containing conjugates were still active in 60% serum while oligoarginine conjugates were not.
null
97
8,255
0
false
null
null
X/B-containing conjugates were still active in 60% serum while oligoarginine conjugates were not.
true
true
true
true
true
1,336
6
DISCUSSION
0
null
null
17,670,797
null
The greater stability of the X/B-containing conjugates to serum enzymes is likely a factor contributing to their high activity.
null
127
8,256
0
false
null
null
The greater stability of the X/B-containing conjugates to serum enzymes is likely a factor contributing to their high activity.
true
true
true
true
true
1,336
6
DISCUSSION
0
null
null
17,670,797
null
The loss of activity in high serum concentrations makes oligoarginine CPPs undesirable as potential therapeutic AO carriers.
null
124
8,257
0
false
null
null
The loss of activity in high serum concentrations makes oligoarginine CPPs undesirable as potential therapeutic AO carriers.
true
true
true
true
true
1,336
7
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-17226957
In summary, we have found that the X/B-containing CPP−PMO conjugates are superior to oligoarginine−PMO conjugates for the following reasons: they display higher activity in cell nuclei, are less affected by serum and are more stable in blood (5).
[ "5" ]
246
8,258
1
false
In summary, we have found that the X/B-containing CPP−PMO conjugates are superior to oligoarginine−PMO conjugates for the following reasons: they display higher activity in cell nuclei, are less affected by serum and are more stable in blood.
[ "5" ]
In summary, we have found that the X/B-containing CPP−PMO conjugates are superior to oligoarginine−PMO conjugates for the following reasons: they display higher activity in cell nuclei, are less affected by serum and are more stable in blood.
true
true
true
true
true
1,337
7
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-17226957
The toxicity of the X/B-containing CPPs can be reduced by keeping the number of X residues below 5 while still maintaining a reasonable delivery efficacy and stability.
[ "5" ]
168
8,259
0
false
The toxicity of the X/B-containing CPPs can be reduced by keeping the number of X residues below 5 while still maintaining a reasonable delivery efficacy and stability.
[]
The toxicity of the X/B-containing CPPs can be reduced by keeping the number of X residues below 5 while still maintaining a reasonable delivery efficacy and stability.
true
true
true
true
true
1,337
7
DISCUSSION
1
5
[ "B5" ]
17,670,797
pmid-17226957
This study provides a basis for further optimization of CPP sequence using R, r, X and B residues in the interest of further reducing toxicity and increasing antisense activity, which will likely lead to more effective AO transporters for potential therapeutic applications.
[ "5" ]
274
8,260
0
false
This study provides a basis for further optimization of CPP sequence using R, r, X and B residues in the interest of further reducing toxicity and increasing antisense activity, which will likely lead to more effective AO transporters for potential therapeutic applications.
[]
This study provides a basis for further optimization of CPP sequence using R, r, X and B residues in the interest of further reducing toxicity and increasing antisense activity, which will likely lead to more effective AO transporters for potential therapeutic applications.
true
true
true
true
true
1,337
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
Protein synthesis requires quality control systems to ensure accuracy between the genetic information carried by messenger RNAs (mRNAs) and the sequence of the corresponding proteins.
[ "1", "2", "3", "4", "5" ]
183
8,261
0
false
Protein synthesis requires quality control systems to ensure accuracy between the genetic information carried by messenger RNAs (mRNAs) and the sequence of the corresponding proteins.
[]
Protein synthesis requires quality control systems to ensure accuracy between the genetic information carried by messenger RNAs (mRNAs) and the sequence of the corresponding proteins.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
In bacteria, when translation proceeds on a truncated mRNA, ribosomes carry on the elongation process until the mRNA 3′-end is reached.
[ "1", "2", "3", "4", "5" ]
135
8,262
0
false
In bacteria, when translation proceeds on a truncated mRNA, ribosomes carry on the elongation process until the mRNA 3′-end is reached.
[]
In bacteria, when translation proceeds on a truncated mRNA, ribosomes carry on the elongation process until the mRNA 3′-end is reached.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
There, translation termination is inefficient and ribosomes stall with the nascent polypeptide chain on the peptidyl-tRNA site (P-site), whereas the aminoacyl-tRNA site (A-site) is empty or only partially filled with the incomplete mRNA (Figure 1A).
[ "1", "2", "3", "4", "5" ]
249
8,263
0
false
There, translation termination is inefficient and ribosomes stall with the nascent polypeptide chain on the peptidyl-tRNA site (P-site), whereas the aminoacyl-tRNA site (A-site) is empty or only partially filled with the incomplete mRNA.
[ "Figure 1A" ]
There, translation termination is inefficient and ribosomes stall with the nascent polypeptide chain on the peptidyl-tRNA site (P-site), whereas the aminoacyl-tRNA site (A-site) is empty or only partially filled with the incomplete mRNA.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
A quality-control mechanism, referred as trans-translation, rescues and recycles the stalled ribosomes and targets the incomplete protein for degradation.
[ "1", "2", "3", "4", "5" ]
154
8,264
0
false
A quality-control mechanism, referred as trans-translation, rescues and recycles the stalled ribosomes and targets the incomplete protein for degradation.
[]
A quality-control mechanism, referred as trans-translation, rescues and recycles the stalled ribosomes and targets the incomplete protein for degradation.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
This process requires a specific RNA acting as both a transfer and a messenger RNA (tmRNA, ssrA or 10Sa RNA).
[ "1", "2", "3", "4", "5" ]
109
8,265
0
false
This process requires a specific RNA acting as both a transfer and a messenger RNA.
[ "tmRNA, ssrA or 10Sa RNA" ]
This process requires a specific RNA acting as both a transfer and a messenger RNA.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
TmRNA has a tRNA (TLD) and a mRNA (MLD)-like domains.
[ "1", "2", "3", "4", "5" ]
53
8,266
0
false
TmRNA has a tRNA (TLD) and a mRNA (MLD)-like domains.
[]
TmRNA has a tRNA (TLD) and a mRNA (MLD)-like domains.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
The TLD is aminoacylated with alanine (Ala) by alanyl-tRNA synthetase (AlaRS) and the MLD is a short (27–105 nt-long) internal open reading frame (ORF).
[ "1", "2", "3", "4", "5" ]
152
8,267
0
false
The TLD is aminoacylated with alanine (Ala) by alanyl-tRNA synthetase (AlaRS) and the MLD is a short internal open reading frame (ORF).
[ "27–105 nt-long" ]
The TLD is aminoacylated with alanine (Ala) by alanyl-tRNA synthetase (AlaRS) and the MLD is a short internal open reading frame (ORF).
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
During trans-translation, alanyl-tmRNA enters the A-site and, despite the lack of codon–anticodon interaction, the incomplete peptide chain is transferred to its alanine.
[ "1", "2", "3", "4", "5" ]
170
8,268
0
false
During trans-translation, alanyl-tmRNA enters the A-site and, despite the lack of codon–anticodon interaction, the incomplete peptide chain is transferred to its alanine.
[]
During trans-translation, alanyl-tmRNA enters the A-site and, despite the lack of codon–anticodon interaction, the incomplete peptide chain is transferred to its alanine.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
Translation then switches to the MLD, which encodes a tag that targets the incomplete protein to degradation.
[ "1", "2", "3", "4", "5" ]
109
8,269
0
false
Translation then switches to the MLD, which encodes a tag that targets the incomplete protein to degradation.
[]
Translation then switches to the MLD, which encodes a tag that targets the incomplete protein to degradation.
true
true
true
true
true
1,338
0
INTRODUCTION
1
2
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
During trans-translation, tmRNA acts in concert with specific ligands [for a recent review, see (1)] including 70S ribosomes, AlaRS (2), small protein B (SmpB) (3), elongation factor Tu (EF-Tu) (4) and ribosomal protein S1 (5).
[ "1", "2", "3", "4", "5" ]
227
8,270
1
false
During trans-translation, tmRNA acts in concert with specific ligands including 70S ribosomes, AlaRS, small protein B (SmpB), elongation factor Tu (EF-Tu) and ribosomal protein S1.
[ "for a recent review, see (1)", "2", "3", "4", "5" ]
During trans-translation, tmRNA acts in concert with specific ligands including 70S ribosomes, AlaRS, small protein B (SmpB), elongation factor Tu (EF-Tu) and ribosomal protein S1.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
Figure 1.Ribosomal protein S1 is dispensable for the tRNA-like function of tmRNA.
[ "1", "2", "3", "4", "5" ]
81
8,271
0
false
Figure 1.Ribosomal protein S1 is dispensable for the tRNA-like function of tmRNA.
[]
Figure 1.Ribosomal protein S1 is dispensable for the tRNA-like function of tmRNA.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
(A) Schematic representation of the first step of trans-translation (trans-peptidation) on polyU mRNAs.
[ "1", "2", "3", "4", "5" ]
103
8,272
0
false
(A) Schematic representation of the first step of trans-translation (trans-peptidation) on polyU mRNAs.
[]
(A) Schematic representation of the first step of trans-translation (trans-peptidation) on polyU mRNAs.
false
false
true
true
false
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
The light gray ovals are the ribosomal subunits (the larger for the 50S and the smaller for the 30S).
[ "1", "2", "3", "4", "5" ]
101
8,273
0
false
The light gray ovals are the ribosomal subunits.
[ "the larger for the 50S and the smaller for the 30S" ]
The light gray ovals are the ribosomal subunits.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
The white ovals are, from right to left, the decoding site (A); the transpeptidyl-site (P) and the exit site (E).
[ "1", "2", "3", "4", "5" ]
113
8,274
0
false
The white ovals are, from right to left, the decoding site (A); the transpeptidyl-site (P) and the exit site (E).
[]
The white ovals are, from right to left, the decoding site (A); the transpeptidyl-site (P) and the exit site (E).
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
tRNAs and tmRNA are depicted as hooks and as a lasso, respectively (for further insights see (1)).
[ "1", "2", "3", "4", "5" ]
98
8,275
0
false
tRNAs and tmRNA are depicted as hooks and as a lasso, respectively ).
[ "for further insights see (1" ]
tRNAs and tmRNA are depicted as hooks and as a lasso, respectively ).
false
true
true
true
false
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
(B) Western blots showing the quasi-absence of S1 in purified ‘S1-free’ 70S ribosomes compared to genuine 70S ribosomes.
[ "1", "2", "3", "4", "5" ]
120
8,276
0
false
(B) Western blots showing the quasi-absence of S1 in purified ‘S1-free’ 70S ribosomes compared to genuine 70S ribosomes.
[]
(B) Western blots showing the quasi-absence of S1 in purified ‘S1-free’ 70S ribosomes compared to genuine 70S ribosomes.
false
false
true
true
false
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
The trans-translation in vitro assay is inactive in the absence of SmpB.
[ "1", "2", "3", "4", "5" ]
72
8,277
0
false
The trans-translation in vitro assay is inactive in the absence of SmpB.
[]
The trans-translation in vitro assay is inactive in the absence of SmpB.
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
(D) Assay of alanine trans-peptidation (asterisk in A), using S1-free 70S ribosomes and increasing amounts of exogenous S1.
[ "1", "2", "3", "4", "5" ]
123
8,278
0
false
(D) Assay of alanine trans-peptidation (asterisk in A), using S1-free 70S ribosomes and increasing amounts of exogenous S1.
[]
(D) Assay of alanine trans-peptidation (asterisk in A), using S1-free 70S ribosomes and increasing amounts of exogenous S1.
false
false
true
true
false
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
Trans-peptidation is monitored by the incorporation of 3H-Ala from alanyl-tmRNA into polyPhe and is normalized to the level of translation, measured in parallel by the incorporation of 14C-Phe (section ‘Experimental procedures’).
[ "1", "2", "3", "4", "5" ]
229
8,279
0
false
Trans-peptidation is monitored by the incorporation of 3H-Ala from alanyl-tmRNA into polyPhe and is normalized to the level of translation, measured in parallel by the incorporation of 14C-Phe (section ‘Experimental procedures’).
[]
Trans-peptidation is monitored by the incorporation of 3H-Ala from alanyl-tmRNA into polyPhe and is normalized to the level of translation, measured in parallel by the incorporation of 14C-Phe (section ‘Experimental procedures’).
true
true
true
true
true
1,338
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5" ]
17,392,345
pmid-16164997|pmid-7524073|pmid-10393194|pmid-10445873|pmid-11101533
The Y-axis represents the quantities (number of pmoles) of 3H alanine incorporated per assay.
[ "1", "2", "3", "4", "5" ]
93
8,280
0
false
The Y-axis represents the quantities (number of pmoles) of 3H alanine incorporated per assay.
[]
The Y-axis represents the quantities (number of pmoles) of 3H alanine incorporated per assay.
true
true
true
true
true
1,338
1
INTRODUCTION
0
null
null
17,392,345
null
Ribosomal protein S1 is dispensable for the tRNA-like function of tmRNA.
null
72
8,281
0
false
null
null
Ribosomal protein S1 is dispensable for the tRNA-like function of tmRNA.
true
true
true
true
true
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
(A) Schematic representation of the first step of trans-translation (trans-peptidation) on polyU mRNAs.
null
103
8,282
0
false
null
null
(A) Schematic representation of the first step of trans-translation (trans-peptidation) on polyU mRNAs.
false
false
true
true
false
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
The light gray ovals are the ribosomal subunits (the larger for the 50S and the smaller for the 30S).
null
101
8,283
0
false
null
null
The light gray ovals are the ribosomal subunits (the larger for the 50S and the smaller for the 30S).
true
true
true
true
true
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
The white ovals are, from right to left, the decoding site (A); the transpeptidyl-site (P) and the exit site (E).
null
113
8,284
0
false
null
null
The white ovals are, from right to left, the decoding site (A); the transpeptidyl-site (P) and the exit site (E).
true
true
true
true
true
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
tRNAs and tmRNA are depicted as hooks and as a lasso, respectively (for further insights see (1)).
null
98
8,285
0
false
null
null
tRNAs and tmRNA are depicted as hooks and as a lasso, respectively (for further insights see (1)).
false
true
true
true
false
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
(B) Western blots showing the quasi-absence of S1 in purified ‘S1-free’ 70S ribosomes compared to genuine 70S ribosomes.
null
120
8,286
0
false
null
null
(B) Western blots showing the quasi-absence of S1 in purified ‘S1-free’ 70S ribosomes compared to genuine 70S ribosomes.
false
false
true
true
false
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
The trans-translation in vitro assay is inactive in the absence of SmpB.
null
72
8,287
0
false
null
null
The trans-translation in vitro assay is inactive in the absence of SmpB.
true
true
true
true
true
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
(D) Assay of alanine trans-peptidation (asterisk in A), using S1-free 70S ribosomes and increasing amounts of exogenous S1.
null
123
8,288
0
false
null
null
(D) Assay of alanine trans-peptidation (asterisk in A), using S1-free 70S ribosomes and increasing amounts of exogenous S1.
false
false
true
true
false
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
Trans-peptidation is monitored by the incorporation of 3H-Ala from alanyl-tmRNA into polyPhe and is normalized to the level of translation, measured in parallel by the incorporation of 14C-Phe (section ‘Experimental procedures’).
null
229
8,289
0
false
null
null
Trans-peptidation is monitored by the incorporation of 3H-Ala from alanyl-tmRNA into polyPhe and is normalized to the level of translation, measured in parallel by the incorporation of 14C-Phe (section ‘Experimental procedures’).
true
true
true
true
true
1,339
1
INTRODUCTION
0
null
null
17,392,345
null
The Y-axis represents the quantities (number of pmoles) of 3H alanine incorporated per assay.
null
93
8,290
0
false
null
null
The Y-axis represents the quantities (number of pmoles) of 3H alanine incorporated per assay.
true
true
true
true
true
1,339
2
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9" ]
17,392,345
pmid-6348874|pmid-375222|pmid-9008164|pmid-7003157
S1, the largest ribosomal protein, binds weakly and reversibly to the head of the 30S ribosomal subunit (6), with an apparent binding constant of 20 nM
[ "6", "7", "8", "9" ]
151
8,291
1
false
S1, the largest ribosomal protein, binds weakly and reversibly to the head of the 30S ribosomal subunit, with an apparent binding constant of 20 nM
[ "6" ]
S1, the largest ribosomal protein, binds weakly and reversibly to the head of the 30S ribosomal subunit, with an apparent binding constant of 20 nM
true
true
false
true
false
1,340
2
INTRODUCTION
1
6
[ "B6", "B7", "B8", "B9" ]
17,392,345
pmid-6348874|pmid-375222|pmid-9008164|pmid-7003157
[(7), and M. Hallier, unpublished Surface Plasmon Resonance data].
[ "6", "7", "8", "9" ]
66
8,292
0
false
.
[ "(7), and M. Hallier, unpublished Surface Plasmon Resonance data" ]
.
false
false
true
true
false
1,340
2
INTRODUCTION
1
8
[ "B6", "B7", "B8", "B9" ]
17,392,345
pmid-6348874|pmid-375222|pmid-9008164|pmid-7003157
S1 consists of six imperfectly repeated motifs, each organized in an oligonucleotide/oligosaccharide binding (OB) fold (8).
[ "6", "7", "8", "9" ]
123
8,293
1
false
S1 consists of six imperfectly repeated motifs, each organized in an oligonucleotide/oligosaccharide binding (OB) fold.
[ "8" ]
S1 consists of six imperfectly repeated motifs, each organized in an oligonucleotide/oligosaccharide binding (OB) fold.
true
true
true
true
true
1,340
2
INTRODUCTION
1
9
[ "B6", "B7", "B8", "B9" ]
17,392,345
pmid-6348874|pmid-375222|pmid-9008164|pmid-7003157
Whereas the first two N-terminal motifs are required for anchoring S1 to the head of the ribosomal small subunit, the four C-terminal motifs face the solvent side (9).
[ "6", "7", "8", "9" ]
167
8,294
1
false
Whereas the first two N-terminal motifs are required for anchoring S1 to the head of the ribosomal small subunit, the four C-terminal motifs face the solvent side.
[ "9" ]
Whereas the first two N-terminal motifs are required for anchoring S1 to the head of the ribosomal small subunit, the four C-terminal motifs face the solvent side.
true
true
true
true
true
1,340
3
INTRODUCTION
1
10
[ "B10", "B5", "B11 B12 B13", "B14", "B15", "B16" ]
17,392,345
pmid-11248028|pmid-11101533|pmid-12457560|pmid-15340139|pmid-15564671|pmid-11593008|pmid-12677067|NA
Protein S1 co-
[ "10", "5", "11–13", "14", "15", "16" ]
14
8,295
0
false
Protein S1 co-
[]
Protein S1 co-
true
true
false
true
false
1,341
3
INTRODUCTION
1
10
[ "B10", "B5", "B11 B12 B13", "B14", "B15", "B16" ]
17,392,345
pmid-11248028|pmid-11101533|pmid-12457560|pmid-15340139|pmid-15564671|pmid-11593008|pmid-12677067|NA
purifies in vivo with an over-expressed tmRNA–SmpB complex (10) and the protein binds tmRNA in vitro with a 10–100 nM apparent binding constant (5,11–13).
[ "10", "5", "11–13", "14", "15", "16" ]
154
8,296
1
false
purifies in vivo with an over-expressed tmRNA–SmpB complex and the protein binds tmRNA in vitro with a 10–100 nM apparent binding constant.
[ "10", "5,11–13" ]
purifies in vivo with an over-expressed tmRNA–SmpB complex and the protein binds tmRNA in vitro with a 10–100 nM apparent binding constant.
false
true
true
true
false
1,341
3
INTRODUCTION
1
10
[ "B10", "B5", "B11 B12 B13", "B14", "B15", "B16" ]
17,392,345
pmid-11248028|pmid-11101533|pmid-12457560|pmid-15340139|pmid-15564671|pmid-11593008|pmid-12677067|NA
Its exact role during trans-translation is unclear.
[ "10", "5", "11–13", "14", "15", "16" ]
51
8,297
0
false
Its exact role during trans-translation is unclear.
[]
Its exact role during trans-translation is unclear.
true
true
true
true
true
1,341
3
INTRODUCTION
1
10
[ "B10", "B5", "B11 B12 B13", "B14", "B15", "B16" ]
17,392,345
pmid-11248028|pmid-11101533|pmid-12457560|pmid-15340139|pmid-15564671|pmid-11593008|pmid-12677067|NA
Conceivably, S1 could prevent degradation of the tmRNA in the cytoplasm before it is loaded onto the ribosome and/or it could be involved in translation resumption onto tmRNA internal ORF, especially since the latter lacks a Shine Dalgarno element (SD) or an initiation codon (in most species, translation resumes onto a...
[ "10", "5", "11–13", "14", "15", "16" ]
337
8,298
0
false
Conceivably, S1 could prevent degradation of the tmRNA in the cytoplasm before it is loaded onto the ribosome and/or it could be involved in translation resumption onto tmRNA internal ORF, especially since the latter lacks a Shine Dalgarno element (SD) or an initiation codon (in most species, translation resumes onto a...
[]
Conceivably, S1 could prevent degradation of the tmRNA in the cytoplasm before it is loaded onto the ribosome and/or it could be involved in translation resumption onto tmRNA internal ORF, especially since the latter lacks a Shine Dalgarno element (SD) or an initiation codon (in most species, translation resumes onto a...
true
true
true
true
true
1,341
3
INTRODUCTION
1
14
[ "B10", "B5", "B11 B12 B13", "B14", "B15", "B16" ]
17,392,345
pmid-11248028|pmid-11101533|pmid-12457560|pmid-15340139|pmid-15564671|pmid-11593008|pmid-12677067|NA
However, S1 stands at the junction of the head, platform and main body of the 30S subunit, at the opposite side of the decoding site (14).
[ "10", "5", "11–13", "14", "15", "16" ]
138
8,299
1
false
However, S1 stands at the junction of the head, platform and main body of the 30S subunit, at the opposite side of the decoding site.
[ "14" ]
However, S1 stands at the junction of the head, platform and main body of the 30S subunit, at the opposite side of the decoding site.
true
true
true
true
true
1,341