NMR studies of backbone-alkylated DNA: duplex stability, absolute stereochemistry, and chemical shift anomalies of prototypal isopropyl phosphotriester modified octanucleotides, (Rp,Rp)- and (Sp,Sp)-(d-[GGA(iPr)ATTCC])2 and -(d-[GGAA(iPr)TTCC])2.
The DNA octamer (d-[GGAATTCC])2 and four alkylated analogues, (Rp)-(d-[GGA(iPr)ATTCC])2, (Sp)-(d-[GGA(iPr)ATTCC])2, (Rp)-(d-[GGAA(iPr)TTCC])2, and (Sp)-(d-[GGAA(iPr)TTCC])2 have been examined using 1H and 31PNMR spectroscopies. Duplex stability, as monitored by both NMR and optical measurements, is shown to be a function of both site and stereochemistry of the phosphotriester moiety. Chemical shift changes relative to the native octamer indicate that there are long-range perturbations in the isopropylated molecules. 1HNMR is shown to be a general means by which stereochemistry at phosphorous can be determined.
Lawrence
D P
DP
Department of Chemistry, Hunter College, New York, NY.
Chen
W Q
WQ
Zon
G
G
Stec
W J
WJ
Uznanski
B
B
Broido
M S
MS
D000477:Alkylating Agents / Q000494:pharmacology*; D000478:Alkylation; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis; D013237:Stereoisomerism
D000477:Alkylating Agents; D009838:Oligodeoxyribonucleotides