HYBRID MOLECULES CONTAINING PROPARGYLIC SULFONES AND DNA MINOR GROOVE-BINDING LEXITROPSINS - SYNTHESIS, SEQUENCE SPECIFICITY OF REACTION WITH DNA AND BIOLOGICAL EVALUATION

A series of hybrids, 4-13, incorporating propargylic sulfones and mino r groove-binding oligopeptide carriers, was synthesized. The anticipat ed preferential binding at adenine sites within the minor groove was c onfirmed by sequencing determination of these agents on high-resolutio n gels, indicating preferential alkylation at guanine, and significant ly, high selectivity for 5'-GACG and 5'-GGTC. The ability of these hyb rids to cleave DNA, as determined by agarose-gel assay, is consistent with the ethidium bromide fluorescence assay. The cytotoxicities of th ese compounds were also determined against human KB cells in vitro. Hi gher cytotoxic activities were observed for the compounds containing f ewer N-methylpyrrole units, an imidazole group and a 2,3-disubstituted naphthyl moiety.