DNA-BASE-PAIR SEQUENCE-SPECIFIC LIGANDS .10. SYNTHESIS AND BINDING TO DNA OF NETROPSIN ANALOGS CONTAINING A COPPER-CHELATING PEPTIDE

Netropsin analogs consisting of two N-propylpyrrolecarboxamide units linked covalently to a copper-chelating peptide Gly-Gly-L-His via two or three glycine residues have been synthesized. Binding to DNA or synthetic polynucleotides has been studied for a netropsin analog in which the linker between Gly-Gly-L-His and the N terminus of the netropsin analog contained three glycine residues (His-Nt). This netropsin analog is shown to chelate a copper ion with 1:1 stoichiometry, similarly to a free Gly-Gly-L-His peptide. This netropsin analog is found to bind with poly(dA) - poly(dT) and poly[d(AT)] . poly[d(AT)] as copper-chelated or free ligand, and to cover three base pairs upon binding. Binding constants and sizes of binding sites for complexes of netropsin analog with DNA, poly (dA) - poly (dT), and poly [d(AT)] . poly [d(AT)] were calculated at [Cu2+]/[His-Nt] ratios equal to zero and unity. Cooperative effects were found in a three-component system containing poly[d(AT)] - poly[d(AT)], His-Nt, and Cu2+-His-Nt, which can be explained by the formation of heterodimers upon interaction of His-Nt and Cu2+-His-Nt at nearest neighboring binding sites.