A comparative conformational study of thymidylyl(3′ → 5′)-thymidine, thymidylyl(3′ → 5′)-5′-thio-5′-deoxythymidine and thymidinylacetomido-[3′(O) →′ (C)]-5′-deoxythymidine

Abstract

A compartive 270 MHz NMR spectroscopic study on the solution structure of the dimer d(TpT) 1, and its two analogues, namely, d(TpST) 2, and NH 2d(TcmT) 4 has been reported. Analysis of chemical shifts and coupling constants indicate that: ( i) The sugar moieties of the constituents nucleotides are not affected by modification of the internucleotide linkages and adopt preferentially and S-type conformation. ( ii) The C4′–C5′ bond in the pT part of the modified dimers 2 and 4 shows a large conformational freedom ( γ + = 32% and 35%, respectively) compared to 1 ( γ + = 75%). ( iii) The population of the trans conformer about C5′–O5′ is less important in d(TpST) 2 compared to d(TpT) 1. The C3′–O3′ bond in 2 adopts a trans conformation as in 1. ( v) The glycosidic bonds in the modified dimers 2 and 4 showed preferential syn conformation. UV and CD data shwo that the modified dimers 2 and 4 have poor tendency to stack intramolecularly, they also base pair less efficiently with d(ApA) as compared to d(TpT) 1.