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Tetraplatinated Artificial Oligopeptides Afford High Affinity Intercalation into dsDNA

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journal contribution
posted on 07.12.2005, 00:00 authored by Lauren A. Levine, Christopher M. Morgan, Kristi Ohr, Mary Elizabeth Williams
This paper reports the binding of an artificial tetrapeptide to which are tethered four Pt(II) complexes (i.e., [Pt(tpy)(py)]48+) with a 12 base pair duplex DNA oligonucleotide. Isothermal Titration Calorimetry reveals that two tetrametallic peptides stoichiometrically bind to each DNA duplex with a binding constant, KB, of 1.7 × 106 M-1, with a change in free energy of −8.5 kcal/mol. This KB represents an affinity 2 orders of magnitude greater than that of the monometallic analogue [Pt(tpy)(pic)]2+ for the same dsDNA sequence. The metalated peptides bind by intercalation into the DNA, partially unwinding the helix while stabilizing the structure, causing an increase in the dsDNA melting temperature of 25 °C.