TY - JOUR
T1 - Oligonucleotide conjugation to a cell-penetrating (tat) peptide by diels-alder cycloaddition
AU - Steven, V.
AU - Graham, D.
N1 - http://suprimo.lib.strath.ac.uk/primo_library/libweb/action/search.do?scp.scps=scope%3A(SU)&srt=rank&tab=local&mode=Basic&dum=true&fn=search&frbg=&dstmp=1270647806478&dscnt=0&ct=search&vid=SUVU01&indx=1&vl(freeText0)=Organic%20%26%20biomolecular%20chemistry&vl(54032236UI0)=lsr02&vl(96071691UI1)=all_items
PY - 2008/10/21
Y1 - 2008/10/21
N2 - Modifed oligonucleotides are routinely employed as analytical probes for use in diagnostics, e.g. in the examination of specific RNA sequences for infectious diseases, however, a major limiting factor in oligonucleotide-based diagnostics is poor cellular uptake of naked oligonucleotides. This problem can be overcome by covalent attachment of a so-called 'cell-penetrating peptide' to form an oligonucleotide peptide conjugate. Stepwise solid phase synthesis of such a conjugate is difficult and expensive due to the conflicting chemistries of oligonucleotides and peptides. A simple approach to overcome this is post-synthetic conjugation. Diels-Alder cycloaddition is an attractive methodology for oligonucleotide peptide conjugation; the reaction is fast, chemoselective and the reaction rate is greatly enhanced in aqueous media - ideal conditions for biological moieties. An oligodeoxyribonucleotide sequence has been derivatised with a series of dienes at the 5′-terminus, using a series of unique dienyl-modified phosphoramidites, and investigation into the effect of diene type on the efficiency of conjugation, using Diels-Alder cycloaddition with a maleimido-derivatised cell-penetrating (TAT) peptide, has been performed. This led to the observation that the optimal diene for conjugation was cyclohexadiene, allowing conjugation of oligodeoxyribonucleotides to a cell-penetrating peptide by Diels-Alder cycloaddition for the first time.
(Taken from Swetswise web site: http://www.swetswise.com/eAccess/viewAbstract.do?articleID=38485673)
AB - Modifed oligonucleotides are routinely employed as analytical probes for use in diagnostics, e.g. in the examination of specific RNA sequences for infectious diseases, however, a major limiting factor in oligonucleotide-based diagnostics is poor cellular uptake of naked oligonucleotides. This problem can be overcome by covalent attachment of a so-called 'cell-penetrating peptide' to form an oligonucleotide peptide conjugate. Stepwise solid phase synthesis of such a conjugate is difficult and expensive due to the conflicting chemistries of oligonucleotides and peptides. A simple approach to overcome this is post-synthetic conjugation. Diels-Alder cycloaddition is an attractive methodology for oligonucleotide peptide conjugation; the reaction is fast, chemoselective and the reaction rate is greatly enhanced in aqueous media - ideal conditions for biological moieties. An oligodeoxyribonucleotide sequence has been derivatised with a series of dienes at the 5′-terminus, using a series of unique dienyl-modified phosphoramidites, and investigation into the effect of diene type on the efficiency of conjugation, using Diels-Alder cycloaddition with a maleimido-derivatised cell-penetrating (TAT) peptide, has been performed. This led to the observation that the optimal diene for conjugation was cyclohexadiene, allowing conjugation of oligodeoxyribonucleotides to a cell-penetrating peptide by Diels-Alder cycloaddition for the first time.
(Taken from Swetswise web site: http://www.swetswise.com/eAccess/viewAbstract.do?articleID=38485673)
KW - oligonucleotide
KW - conjugation
KW - cell-penetrating (tat) peptide
KW - diels-alder cycloaddition
UR - http://www.swetswise.com/eAccess/viewAbstract.do?articleID=38485673
UR - http://dx.doi.org/10.1039/b807843b
U2 - 10.1039/b807843b
DO - 10.1039/b807843b
M3 - Article
SN - 1477-0520
VL - 6
SP - 3781
EP - 3787
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 20
ER -