Structural Features Of 2′,3′-Riboanhydroadenosine, A Conformationally Restricted Termination Substrate Of DNA Polymerases

Abstract

2′,3′-Riboanhydroadenosine (raA), a conformationally restricted inhibitor of some DNA polymerases, has been studied by X-Ray crystallography. It crystallizes in space group P1 with unit cell parameters: a=4.834(1); b=6.893(1); c=15.942(2)Å; α=90.51(1); β=97.16(2); γ=89.27(2)^[ddot]; V=527.1α³ and with two independent molecules (A and B) in the cell. The conformation of A and B molecules about the glycosidic bond is different. In the A molecule, the glycosidic torsion angle χ^A is 56.8^[ddot] and corresponds to syn conformation; in the B molecule, χ^B=−170.8^[ddot], which corresponds to the nucleoside in anti conformation. The sugar rings of both molecules are slightly puckered (0.1Å), C1′ being exo in A and C4′ -endo-04′-exo in B. The conformation of A and B molecules about the exocyclic bond C4′-C5′ is gauche⁺. The observed similarities in some structural and biochemical properties of 2′,3′-riboanhydronucleosides and 2′,3′-dideoxy-2′,3′-didehydronucleosides are discussed.