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 hav e? 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 u sed as the 5'-protecting group because of incompatibility of the cyano borane moiety with 5'-DMT cations generated during the deprotection st ep, The presence of the cyanoborane group was confirmed on the basis o f Fab-MS and H-1 NMR spectroscopy, The H-8 proton of (7b)dG in the din ucleotides shifted 0.35-0.80 p.p.m. downfield relative to that of unmo dified 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 increas es the acidity of the H-8 proton of (7b)dG, These studies illustrate t he feasibility of synthesizing boron-containing oligonucleotides which are modified at the N-7-guanine to block Hoogsteen pairing in the DNA major groove.