Syntheses of heterocyclic ethenyl C-nucleosides for recognition of inverted base pairs within the DNA triple helix by stereoselective intramolecular cyclization and olefin metathesis.
Canonical recognition of gene sequences would allow precise means for specific genetic intervention. Unfortunately, specific recognition of two of the four possible base pairs by triplex-forming oligonucleotide (TFO) as X x T-A and Y x C-G within a triplex currently remains elusive. A series of C1-ethenyl nucleosides have been devised and evaluated extensively for stability and specificity by molecular dynamics simulation. A synthesis via olefin metathesis of the unprotected heterocycle and a conveniently prepared anomerically pure C1-vinyl 2-deoxyribofuranose is presented as a significant improvement over a previously reported strategy.
Rothman
Jeffrey H
JH
Division of Experimental Therapeutics, Department of Medicine, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA. jhr21@columbia.edu
D000475:Alkenes / Q000737:chemistry*; D020029:Base Pairing; D003500:Cyclization; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D000475:Alkenes; D006571:Heterocyclic Compounds; D009705:Nucleosides; C051802:triplex DNA; D004247:DNA