Base-boronated dinucleotides: synthesis and effect of N7-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 N7-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 1H 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 D20 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 N7-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 N7-guanine to block Hoogsteen pairing in the DNA major groove.
Hasan
A
A
Department of Chemistry, P.M. Gross Chemical Laboratory, Duke University, Durham, NC 27708-0346, USA.
Li
H
H
Tomasz
J
J
Shaw
B R
BR
D000577:Amides / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D003903:Deuterium; D005449:Fluorenes; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D010756:Phosphoric Acids / Q000737:chemistry; D011522:Protons; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000577:Amides; D001896:Boron Compounds; D005449:Fluorenes; D009711:Nucleotides; D010756:Phosphoric Acids; D011522:Protons; D004247:DNA; C011067:phosphoramidic acid; D003903:Deuterium; D003849:Deoxyguanosine; D001895:Boron