Base-boronated dinucleotides: Synthesis and effect of N-7-cyanoborane substitution on the base protons

Boron-modified nucleic acids comprise a new Set of DNA mimics that have? potential biological and therapeutic applications, A series of nine dinucleotides containing N-7-cyanoborane-2'deoxyguanosine ((7b)dG) at the 3', 5' or both positions of the phosphodiester linkage have been synthesized using solution phase phosphoramidite chemistry, Fmoc was used as the 5'-protecting group because of incompatibility of the cyanoborane moiety with 5'-DMT cations generated during the deprotection step, The presence of the cyanoborane group was confirmed on the basis of Fab-MS and H-1 NMR spectroscopy, The H-8 proton of (7b)dG in the dinucleotides shifted 0.35-0.80 p.p.m. downfield relative to that of unmodified dG. A comparison of the D2O exchange kinetics of the H-8 proton at 60 degrees C showed that H-8 of (7b)dG is very labile relative to unmodified dG,indicating that the N-7-cyanoborane modification increases the acidity of the H-8 proton of (7b)dG, These studies illustrate the feasibility of synthesizing boron-containing oligonucleotides which are modified at the N-7-guanine to block Hoogsteen pairing in the DNA major groove.