Knobler R M, Radlwimmer F B, Lane M J
Second Department of Dermatology, University of Vienna, Austria.
Nucleic Acids Res. 1992 Sep 11;20(17):4553-7. doi: 10.1093/nar/20.17.4553.
The relative degree of both equilibrium binding and of ultraviolet light induced adduct formation for the antitumor antibiotic gilvocarin V with two hexaecamer DNA sequence isomers, d[ATATATAGCTATATAT]2 and d[AAAAAAAGCTTTTTTT]2, was assessed. The experiments reveal that gilvocarin V binds, under equilibrium conditions, and reacts, in the presence of exogenously applied UV light, more efficiently with the alternating purine:pyrimidine sequence hexadecamer than the homopurine:homopyrimidine duplex at identical gilvocarcin V to DNA duplex ratios. DNAse I digests of adduct containing duplexes derived from the d[AAAAAAAGCTTTTTTT]2 duplex, identified and isolated using gel shift assays employing denaturing polyacrylamide gels, confirm that gilvocarcin V adducts can be formed with thymine residues but suggest that adduct formation with either adenine or guanine residues is also possible.
评估了抗肿瘤抗生素吉尔vocarin V与两种六聚体DNA序列异构体d[ATATATAGCTATATAT]2和d[AAAAAAAGCTTTTTTT]2的平衡结合程度以及紫外线诱导加合物形成的相对程度。实验表明,在相同的吉尔vocarin V与DNA双链体比例下,吉尔vocarin V在平衡条件下结合,并在外源施加紫外线的情况下与交替嘌呤:嘧啶序列十六聚体比同型嘌呤:同型嘧啶双链体更有效地反应。使用变性聚丙烯酰胺凝胶的凝胶迁移分析鉴定并分离了源自d[AAAAAAAGCTTTTTTT]2双链体的含加合物双链体的DNA酶I消化物,证实吉尔vocarin V加合物可以与胸腺嘧啶残基形成,但表明与腺嘌呤或鸟嘌呤残基形成加合物也是可能的。