A series of binuclear DNA-binding ligands was prepared by linking two (2,2′:6′,2″-terpyridine)platinum(II) moieties via alpha omega-dithiols of the type HS-[CH2]n-SH where n = 4-10. A monomeric analogue was also synthesized. Compounds were characterized by elemental analysis and electronic and n.m.r. spectroscopy. Viscometric measurements with sonicated rod-like DNA fragments and covalently closed circular DNA were performed to investigate the mode of binding of these agents. The ligands with n = 5 and 6 function as bis intercalators and form a single ‘base-pair sandwich’ in violation of neighbour-exclusion binding. Bifunctional reaction occurs for the ligand with n = 7, whereas the ligands with n = 8 and 10 show a preference for mixed monofunctional/bifunctional binding. The data do not permit definitive assignment of the binding mode of the ligands with n = 4 and 9. All compounds are growth-inhibitory against mouse leukaemia L1210 cells in culture with IC50 values in the range 2-14 microM.
Binuclear platinum (II)-terpyridine complexes. A new class of bifunctional DNA-intercalating agent
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W D McFadyen, L P G Wakelin, I A G Roos, B L Hillcoat; Binuclear platinum (II)-terpyridine complexes. A new class of bifunctional DNA-intercalating agent. Biochem J 15 September 1986; 238 (3): 757–763. doi: https://doi.org/10.1042/bj2380757
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