Phosphate-Methylated DNA Fragments Involved in Parallel and Antiparallel Duplex Formation Novel Aspects of Structure Stability and Biological Activity

Abstract

Abstract Parallel duplexes are encountered for the phosphate-methylated DNA dinucleotides d(CpC) and d(TpC; for the Sp configuration exclusively. since inward location of the methyl group (Rp,) encounters severe steric interactions in the groove. A parallel duplex with T-T base pairs is found for the natural system d(T10) only after complexation of the cationic peptides polylysine and polyornithine with the phosphate groups, which diminishes phosphate-phosphate repulsions. For natural d(C10), parallel duplex formation is seen exclusively after complexation with polylysine, which only uses pro-S phosphate oxygens in the complexation. Polyornithine complexates with both pro-S and pro-R phosphate oxygens, leading to steric hindrance in the groove of the C-C duplex. For antiparallel duplexes of phosphate-methylated DNA (‘antisense’) with natural polynucleotides (‘sense’) it is found that the hybridization has a cooperative character. Furthermore, it is mentioned that long phosphate-methylated DNA fragments ca...