PROBING NUCLEIC-ACID GEOMETRIES - OLIGONUCLEOTIDES CONTAINING 2'-O-PHENETHYLADENOSINE AT SPECIFIC SITES

The synthesis of 2'-O-phenethyladenosine and its incorporation into an oligodeoxyribonucleotide and a chimeric oligodeoxy/oligoribonucleotid e are described. The study was designed to determine the consequences of site-specific induction of such a small, flexible hydrophobic ligan d into a nucleic acid. Through the use of optical (T-m, circular dichr oism) spectroscopy and nuclear magnetic resonance, it was discovered t hat this substitution destabilized the duplex and that the benzene rin g of the phenethyl group lies in the major groove of both the DNA anal og and the DNA-RNA duplex structure. The plane of the benzene ring lie s perpendicular to the stacked bases of the oligonucleotide which, in other respects, exhibits relatively normal B-type geometry for the oli godeoxynucleotide and a modified A-type geometry in the DNA-RNA duplex . This finding has implications for the synthesis of oligodeoxynucleot ides containing major groove binders as ligands.