CRYSTAL-STRUCTURE OF GAMMA-OXAPENTAMIDINE COMPLEXED WITH D(CGCGAATTCGCG)(2) - THE EFFECTS OF DRUG STRUCTURAL-CHANGE ON DNA MINOR-GROOVE RECOGNITION

The crystal structure of the complex of gamma-oxapentamidine and the D NA dodecamer d(CGCGAATTCGCG), has been determined to a resolution of 0 .22 nm and an R factor of 18.9%. The gamma-oxapentamidine ligand inter acts with the dodecamer by classic minor groove binding via interactio ns within the A+T-rich region of the minor groove. A chain of solvent molecules lies along the mouth of the minor groove on the outside of t he bound ligand. The structural details of the complex are discussed a nd compared with the closely analogous complex with pentamidine bound to the same dodecamer [Edwards, K. J., Jenkins, T. C. and Neidle, S. ( 1992) Biochemistry 31, 7104-7109]. The amidinium groups of the ligand do not hydrogen bond to bases, but are in close contact with O4' sugar ring atoms. This in part explains the reduced DNA binding affinity of this ligand compared to pentamidine.