The sugars in chromomycin A3 stabilize the Mg(2+)-dimer complex.

Chromomycin A3 (CRA3) is a glycosylated antitumor antibiotic that binds as a dimer to the minor groove of DNA, with a Mg2+ cation (or another divalent cation with a radius less than 0.85 A) forming the center of the dimer. It has been shown that the chromose sugars are necessary for DNA binding [Kaziro & Kamiyama (1967) J. Biochem. (Tokyo) 62, 424-429; Kamiyama (1968) J. Biochem. (Tokyo) 63, 566-572], although the reason for this has not been addressed. We have investigated the role that the chromose sugars play in metal complexation in solution (methanol) by comparing the optical behavior of CRA3 and its aglycon, CRN, in the presence of various divalent metals (Mg2+, Ni2+, and Ca2+). The results show that CRA3 forms a dimeric complex [i.e., (CRA3)2M, where M is a metal ion] in the presence of 1 mol equiv of either Ni2+ or Mg2+ but a 1:1 complex in the presence of the much larger Ca2+. In contrast, CRN forms a 1:1 complex (CRN.M)+ with all three metals under identical conditions (1:1 mole ratio of drug to metal). Thus, for the smaller metal ions the sugars stabilize the 2:1 CRA3-metal complex in solution. NMR data on the 2:1 CRA3-Mg2+ complex show that the trisaccharide of one CRA3 molecule lies in close proximity to the chromophore of the other CRA3 molecule. This interaction, which is also present in the Mg(2+)-CRA3-DNA complex [Gao & Patel (1989) Biochemistry 28, 751-762], appears to be related to the stability of the dimer in solution.(ABSTRACT TRUNCATED AT 250 WORDS)