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/oligoribonucleotide are described. The study was designed to determine the consequences of site-specific induction of such a small, flexible hydrophobic ligand into a nucleic acid. Through the use of optical (Tm, circular dichroism) spectroscopy and nuclear magnetic resonance, it was discovered that this substitution destabilized the duplex and that the benzene ring of the phenethyl group lies in the major groove of both the DNA analog and the DNA-RNA duplex structure. The plane of the benzene ring lies perpendicular to the stacked bases of the oligonucleotide which, in other respects, exhibits relatively normal B-type geometry for the oligodeoxynucleotide and a modified A-type geometry in the DNA-RNA duplex. This finding has implications for the synthesis of oligodeoxynucleotides containing major groove binders as ligands.
Deshmukh
H M
HM
Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112, USA.
Broom
A D
AD
D000241:Adenosine / Q000031:analogs & derivatives*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003854:Deoxyribonucleotides; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D012265:Ribonucleotides; D013329:Structure-Activity Relationship
C099577:2'-O-phenethyladenosine; D003854:Deoxyribonucleotides; D009841:Oligonucleotides; D012265:Ribonucleotides; D000241:Adenosine