SYNTHESIS AND CONFORMATIONAL STUDIES OF D(TPA) AND R(UPA) CONJUGATED WITH HISTAMINE AND ETHYLENEDIAMINE

Dinucleotides (Figure 1b-d) possessing histamino/ethylenediamino subst ituents at C8 of adenine have been synthesised for modelling the molec ular interactions that occur at catalytic site of nucleases. These com pounds have been designed for putative molecular recognition of intern ucleotide phosphate by a complementary group (imidazole/-NH2) in the p endant C-8 side chains. H-1 NMR spectroscopic analysis of synthesised model compounds indicate that C-8 modification leads to increase in pe rcentage of S conformation of modified sugar while still maintaining a n anti glycosyl torsion as in unmodified analog d(TpA). The C-8 side c hain functionality (histamine/ethylenediamine) is probably involved in intramolecular interaction (electrostatic/ hydrogen bond) with the ph osphate and/or 2'OH in (14). Such predisposition of side chain catalyt ic groups is important in developing appropriate models for active sit e of nucleases.