Controlling gene expression by zinc(II)-macrocyclic tetraamine complexes.

Abstract The zinc(II) complexes of 12-membered macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two aryl-methyl group(s) (quinolyl-methyl, naphthyl-methyl, and acridinyl-methyl) selectively bind to thymines in a TATA box of the SV40 early promoter region and thus inhibit the binding of a transcriptional factor, TATA binding protein. These Zn 2+ –cyclen derivatives also act as inhibitors of DNA-targeted enzymes, type I and type II topoisomerases. They also exhibited strong antimicrobial activities for the Gram-positive bacterial strain. These biochemical and biological properties were compared with those of conventionally established AT-recognizing drugs, distamycin A and DAPI. The Zn 2+ –cyclen complexes are a new type of small molecular, genetic transcriptional regulation factor.