High-throughput chemical modification of oligonucleotides for systematic structure-activity relationship evaluation.
Chemical modification of siRNA is achieved in a high-throughput manner (96-well plate format) by copper catalyzed azide-alkyne cycloadditions. This transformation can be performed in one synthetic operation at up to four positions with complete specificity, good yield, and acceptable purity. As demonstrated here, this approach extends the current synthetic options for oligonucleotide modifications and simultaneously facilitates the systematic, rapid biological evaluation of modified siRNA.
Department of Process Chemistry, Merck Research Laboratories , Rahway, New Jersey 07065, United States.
Daniel
D
Zewge
Francis
F
Gosselin
Denise M
DM
Kenski
Jenny
J
Li
Vasant
V
Jadhav
Yu
Y
Yuan
Sandhya S
SS
Nerurkar
David M
DM
Tellers
W Michael
WM
Flanagan
Ian W
IW
Davies
D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology; D060327:Solid-Phase Synthesis Techniques; D013329:Structure-Activity Relationship
D000480:Alkynes; D001386:Azides; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D003300:Copper