Duplex Stabilization of DNA: Oligonucleotides containing 7‐substituted 7‐deazaadenines

Abstract

Abstract The oligonucleotide building blocks 4b–d derived from 7‐bromo‐, 7‐chloro‐, and 7‐methyl‐substituted 7‐deaza‐2′‐deoxyadenosines 3b–d were prepared. They were employed in the solid‐phase synthesis of the oligonucleotides 7–25 . The dA residues of the homomer d(A 12 ), the alternating d[(A‐T) 6 ], and the palindromic d(G‐T‐A‐G‐A‐A‐T‐T‐C‐T‐A‐C) were replaced by 3b–d as well as by the parent 7‐deaza‐2′‐deoxyadenosine ( 3a ). The melting profiles and CD spectra of oligonucleotide duplexes, showing this major groove modification, were measured, and the T m values as well as the thermodynamic data were determined. It was found that small substituents such as Br, Cl, or Me introduced in the 7‐position of a 7‐deazaadenine residue increase the duplex stability compared to oligonucleotides containing adenine.