Crystallization and preliminary X-ray analysis of anti-cancer agent 3-(9-acridinylamino)-5-(hydroxymethyl)aniline complexed with the DNA hexamer d(CGTACG)(2).

摘要

3-(9-Acridinylamino)-5-(hydroxymethyl)aniline (AHMA) is an anti-cancer agent with significant efficacy against murine leukemia and solid tumors. As a DNA topoisomerase inhibitor, AHMA is proposed to form a ternary complex with DNA and topoisomerase and bind to DNA in an intercalative manner. In order to understand the interactions between AHMA and DNA and study the structure-function relationship of amsacrine analogue, the AHMA-d(CGTACG)(2) complex was crystallized using the sitting-drop vapor-diffusion method. The native crystals diffract to 2.9-A resolution and belong to space group P3(1)21 or P3(2)21 with unit-cell parameters a=b=57.52, c=122.17 A when analyzed using Cu Kalpha radiation. Patterson map indicates that in the crystal, the directions of the DNA base stacking are nearly perpendicular to the c-axis of the crystal unit cell.