2-脱氨基放线菌素D，合成及其与脱氧核糖核酸的相互作用。

2-Deaminoactinomycin D, synthesis and interaction with deoxyribonucleic acid.

作者信息

Mosher C W, Kuhlmann K F, Kleid D G, Henry D W

出版信息

J Med Chem. 1977 Aug;20(8):1055-9. doi: 10.1021/jm00218a013.

Abstract

2-Deaminoactinomycin D has been synthesized and characterized. It binds to DNA by intercalation according to NMR, CD, thermal denaturation, and unwinding studies on the drug-DNA complex. Loss of the 2-amino group does not seriously affect binding parameters relative to actinomycin D; affinity for calf thymus DNA may even be increased, according to deltaTm measurements. The unwinding of circular DNA caused by this compound is at least as large as that effected by actinomycin D and ethidium bromide. Nevertheless, 2-deaminoactinomycin D is less effective than actinomycin D in inhibiting nucleic acid syntheses in L1210 cell culture and in in vivo antitumor activity against P388 leukemia.

摘要

2-脱氨基放线菌素D已被合成并进行了表征。根据对药物-DNA复合物的核磁共振（NMR）、圆二色性（CD）、热变性和解链研究，它通过嵌入作用与DNA结合。相对于放线菌素D，2-氨基的缺失并未严重影响结合参数；根据熔解温度变化（deltaTm）测量，其对小牛胸腺DNA的亲和力甚至可能增加。该化合物引起的环状DNA解链至少与放线菌素D和溴化乙锭所引起的一样大。然而，在L1210细胞培养中抑制核酸合成以及对P388白血病的体内抗肿瘤活性方面，2-脱氨基放线菌素D比放线菌素D的效果要差。