Crystal Structures of Four A-DNA Decamers that Contain C5-Propyne-Cytosines

Abstract

Nucleic acids incorporating C5-propynepyrimidines have significantly-increased stability which is valuable for antisense applications. Crystal structures of four variants of the d(ACCGGCCGGT) decamer, with each cytosine individually replaced by a C5-propynecytosine (abbreviated Y), have been analyzed at high resolution in an attempt to understand the structural basis of the stabilization effect by this novel chemical modification. The five independent NpY dinucleotide steps in these four structures show that the hydrophobic propyne group is extensively stacked with the 5′-side base. A model of the poly(purine):poly(C5-propynepyrimidine) A-DNA duplex shows that the deep major groove is substantially filled up by the C5-propyne groups from the poly(C5-propynepyrimidine) strand, displacing many water molecules. These observations may explain the enhanced stability of the duplex incorporating C5-propynepyrimidines.