ANTITUMOR ANTIBIOTICS--CC-1065 AND THE DUOCARMYCINS

描述：(首席调查者的)CC-1065和 描述了一种特别有效的抗肿瘤抗生素--双环素类抗生素。 CC-1065和双霉素通过一种 双链DNA的序列选择性烷基化是通过可逆的， 立体电子控制腺嘌呤N3与最少取代基的加成 小槽5或3.5碱基对内的活性环丙烷的碳 富含AT的站点。进一步研究以确定这些特征 来确定DNA烷基化反应的起源 选择性和催化的来源，并定义基本 结构、化学或物质之间关系的基本原理 功能反应性、DNA烷基化特性和生物活性 都是很详细的。

DESCRIPTION: (Principal Investigator's) A detailed study of CC-1065 and the duocarmycins, exceptionally potent antitumor antibiotics, are described. CC-1065 and the duocarmycins derive their biological properties through a sequence selective alkylation of duplex DNA which proceeds by reversible, stereoelectronically-controlled adenine N3 addition to the least substituted carbon of the activated cyclopropane within minor groove 5 or 3.5 base pair AT-rich sites, respectively. Further studies to define the characteristics of the alkylation reaction, to determine the origin of the DNA alkylation selectivity and the source of catalysis, and to define fundamental principles underlying the relationships between structure, chemical or functional reactivity, DNA alkylation properties, and biological activity are detailed.