Raney V M, Harris T M, Stone M P
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Chem Res Toxicol. 1993 Jan-Feb;6(1):64-8. doi: 10.1021/tx00031a010.
The binding of aflatoxin B1 to DNA and DNA adduction by aflatoxin B1 exo-8,9-epoxide were studied as a function of DNA conformation. Equilibrium binding of aflatoxin B1 to A-, B-, and Z-form helices was monitored by measurement of NMR linewidth for the methoxy protons of aflatoxin B1. The data revealed that as compared to B-form DNA, the association of aflatoxin with the A-form helix is significantly reduced. No binding to Z-DNA was observed. The yields obtained following reaction of the respective monomers with aflatoxin B1 exo-8,9-epoxide revealed that only dG forms an adduct. The reactivity of aflatoxin B1 exo-8,9-epoxide with single-strand DNA was determined via constant-temperature experiments in which the yield of adduct was measured for a family of oligonucleotides of increasing thermal stability. The results demonstrate that duplex structure favors adduct formation. Adduct yields were compared for A-, B-, and Z-form helices. About 12 times less adduct is produced from the A-form helix as compared to B-form, while no adduct is produced from a Z-form duplex. The results support the conclusion that reaction of aflatoxin B1 exo-8,9-epoxide with DNA proceeds via an intercalated transition-state complex only with the B-form double helix.
研究了黄曲霉毒素B1与DNA的结合以及黄曲霉毒素B1外-8,9-环氧化物对DNA的加合作用，并将其作为DNA构象的函数进行研究。通过测量黄曲霉毒素B1甲氧基质子的NMR线宽来监测黄曲霉毒素B1与A-、B-和Z-型螺旋的平衡结合。数据显示，与B型DNA相比，黄曲霉毒素与A型螺旋的结合显著减少。未观察到与Z-DNA的结合。各自单体与黄曲霉毒素B1外-8,9-环氧化物反应后获得的产率表明，只有dG形成加合物。通过恒温实验确定了黄曲霉毒素B1外-8,9-环氧化物与单链DNA的反应活性，在该实验中，测量了一系列热稳定性不断增加的寡核苷酸的加合物产率。结果表明，双链结构有利于加合物的形成。比较了A-、B-和Z-型螺旋的加合物产率。与B型相比，A型螺旋产生的加合物减少约12倍，而Z型双链体未产生加合物。结果支持以下结论：黄曲霉毒素B1外-8,9-环氧化物与DNA的反应仅通过与B型双螺旋的插入过渡态复合物进行。
