Berman E, Kam M
Organic Chemistry Department, Weizmann Institute of Science, Rehovot, Israel.
Prog Clin Biol Res. 1989;289:217-27.
The solution conformations of chromomycin A3 (CRA) and dechromose-A chromomycin A3 (CRA-B) in dichloromethane and methanol were studied by two-dimensional (2D) NMR techniques. In dichloromethane, the drugs are found in a compact wedged-like conformation, with the phenolic hydroxyls at the tip and the side chains folded back to one side of the aglycon plane, oriented parallel to each other. The overall structure is stabilised by intramolecular hydrogen bonds and by the formation of a hydrophobic pocket, enclosed by the three side chains. In methanol, the drugs have the expected open conformation with extended side chains. Like its parent drug, CRA-B binds to d(ATGCAT)2 duplex with a major groove orientation, a 2:1 drug/duplex ratio and a two-fold symmetry of the resultant complex. The drug molecule is suggested to reside diagonally across the two strands of the duplex and to span 3 base pairs, while all three side chains of the drug are folded away from the major groove of the DNA. The observed nonequivalent positions of CRA and CRA-B within the major groove of the duplex results from the different conformation adopted by the sugar side-chains in the two complexes.
采用二维（2D）核磁共振技术研究了嗜癌霉素A3（CRA）和去糖基-A嗜癌霉素A3（CRA-B）在二氯甲烷和甲醇中的溶液构象。在二氯甲烷中，发现这两种药物呈紧密的楔形构象，酚羟基位于顶端，侧链折回到苷元平面的一侧，彼此平行排列。整体结构通过分子内氢键以及由三条侧链围成的疏水口袋的形成而得以稳定。在甲醇中，药物具有预期的开放构象，侧链伸展。与母体药物一样，CRA-B以大沟方向、2:1的药物/双链体比例和所得复合物的二重对称性与d(ATGCAT)2双链体结合。药物分子被认为对角横跨双链的两条链，跨越3个碱基对，而药物的所有三条侧链都从DNA的大沟折回。双链体大沟内CRA和CRA-B观察到的不等价位置是由两种复合物中糖侧链所采用的不同构象导致的。
