G-quadruplexes (G4) exhibit potent inhibitions to telomerase and expression of oncogenes.1 Therefore, small molecules that promote the formation and/or stabilize G-quadruplex structures has become promising candidates for anticancer drugs.2 Pt(II) complexes with extended aromatic ligands provide p-surfaces that are compatible with G-quartet and can significantly stabilize G4. However, current Pt(II) based G4 stabilizers often suffer from poor selectivity to G4 over duplex DNA. Herein, we report the synthesis and G4 binding abilities   of several Pt(II) complexes with different functionalized diamine ligands [PtII(bpy)(N^N)]2+ (bpy=2,2'-bipyridine, N^N= 3,4-benzo[a]phenazine diamine or 5,6-chrysene diamine). Chrysene diamine is expected to limit the binding of Pt complexes to duplex DNA due to its bulky size.3,4 The interactions between variety of G4 topological structures and the complexes were evaluated by circular dichroism spectroscopy, UV-Melting, polymerase chain reaction stop assay, nuclear magnetic resonance, and molecular modeling studies. All the complexes stabilize G-quadruplex and show high selectivity to G4 over duplex DNA. Furthermore, introduction of a positive charged side chains to either ancillary or chrysene ligands can improve the selectivity to G4 polymorphism. Balasubramanian S., Neidle S. Curr. Opin. Chem. Biol. 2009 , 13, 345. Jackson B. A.; Barton J. K. J. Am. Chem. Soc. 1997 ,  119, 12986. Zeglis B. M.; Barton J. K. Nature protocols. 2007 , 2, 357.

Platinum(II)-diamine complexes promote the formation of G-quadruplex

243rd National Meeting (2012)

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