title: Chelating, DNA-binding and DNA-cleaving properties of a synthetic model for bleomycin.
abstract: We have previously described a simplified model of the complexing part of bleomycin, namely methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), and disubstituted bithiazoles structurally related to the 'tripeptide S' moiety of bleomycin. The present work is devoted to the study of a new derivative, [3-[2-[2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidyl-3 -aminobutyryl-glycyl]-2',4-bithiazole-4-carboxamido]-propyl]- dimethylsulphonium iodide (AMBI-A2), which includes both AMPHIS and a judiciously chosen synthetic bithiazole. This compound, the synthesis of which is described here, has been shown to mimic the chelating and binding properties of the parent drug bleomycin A2, but to cleave DNA at higher concentration.
mesh_terms: D001761:Bleomycin / Q000138:chemical synthesis / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D005609:Free Radicals; D008961:Models, Structural; D014783:Viscosity
chemical_list: D002614:Chelating Agents; D005609:Free Radicals; D001761:Bleomycin; D004247:DNA