Synthesis and conformational studies of d(TpA) and r(UpA) conjugated with histamine and ethylenediamine

Abstract

Dinucleotides (Figure 1b-d) possessing histamino/ethylenediamino substituents at C8 of adenine have been synthesised for modelling the molecular interactions that occur at catalytic site of nucleases. These compounds have been designed for putative molecular recognition of internucleotide phosphate by a complementary group (imidazole/-NH₂) in the pendant C-8 side chains. ¹H NMR spectroscopic analysis of synthesised model compounds indicate that C-8 modification leads to increase in percentage of S conformation of modified sugar while still maintaining an anti glycosyl torsion as in unmodified analog d(TpA). The C-8 side chain functionality (histamine/ethylenediamine) is probably involved in intramolecular interaction (electrostatic/ hydrogen bond) with the phosphate and/or 2'OH in (14). Such predisposition of side chain catalytic groups is important in developing appropriate models for active site of nucleases. Dinucleotides d(TpA) and r(UpA) conjugated at C8 (A) with histamino/ethylenediamino substituents have been synthesized for modelling the molecular interactions that occur at catalytic site of nucleases. ¹H and ³¹P-NMR analysis indicate that an increase in percentage of S conformers of modified sugar residue, while maintaining anti-glycosyl torsion. The results have importance in rational design of appropriate models for active site of nucleases.