Gilvocarcin V exhibits both equilibrium DNA binding and UV light induced DNA adduct formation which is sequence context dependent

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Abstract
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.