X-ray crystallographic studies of small molecules and their interaction with DNA.

摘要

X-ray crystallography and molecular mechanics were used to study the three-dimensional structure of three small molecules, one drug-DNA complex, and several metal ion-DNA complexes.;Structural features of the d(CGCGCGCGCGCG)-ditercalinium complex have been inferred by geometric and energetic analysis using molecular mechanics. A systematic comparison of the dodecamer model complex with the d(CGCG)-ditercalinium crystal structure and B-form DNA have been made. The driving force that stabilizes the complex is the interaction between the chromophores of ditercalinium and bases of DNA. Molecular features of the complex that are possibly responsible for the drug's unique mechanism, include the accessibility of the minor groove, the bend in the helical axis, the rigidity of linker, and the introduced asymmetry parameters.;X-ray crystallography was used to obtain the structure of three organic molecules. In (2s,3r,4s,5s)-3-(allyloxy)-4- (n-(benzyloxycarbonyl)-amino) -5,6-dihydroxy-2- (1-(allyoxy)naphth-3-yl) -2-hexanol structure, the ;Features of the cation-DNA interactions that stabilize the DNA crystal structure have been inferred from the x-ray crystallography structure of the hexanucleotide d(CGCGCG) at 1.3A high-resolution (structure I). Cation binding sites and DNA solvation have been visualized in great detail. The crystal structure displays substantial solvent and solute order; the hydrated magnesium complexes exhibit specific contacts with DNA and there is only one conformation (ZI). This contrasts with the identical hexamer crystallized using a higher ionic strength mixed salt buffer (structure II). Structure II exhibits greater solvent and solute disorder, less well defined cation-DNA contacts and two conformations (ZI and ZII) of the Z-form nucleic acid.