| Autor: |
He CC; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Hamlow LA; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Roy HA; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Devereaux ZJ; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Hasan MA; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Israel E; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Cunningham NA; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Martens J; Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, 6525 ED Nijmegen, The Netherlands., Berden G; Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, 6525 ED Nijmegen, The Netherlands., Oomens J; Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, 6525 ED Nijmegen, The Netherlands.; Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands., Rodgers MT; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States. |
| Abstrakt: |
Despite its success as an anticancer drug, cisplatin suffers from resistance and produces side effects. To overcome these limitations, amino-acid-linked cisplatin analogues have been investigated. Lysine-linked cisplatin, Lysplatin, (Lys)PtCl 2 , exhibited outstanding reactivity toward DNA and RNA that differs from that of cisplatin. To gain insight into its differing reactivity, the structure of Lysplatin is examined here using infrared multiple photon dissociation (IRMPD) action spectroscopy. To probe the influence of the local chemical environment on structure, the deprotonated and sodium-cationized Lysplatin complexes are examined. Electronic structure calculations are performed to explore possible modes of binding of Lys to Pt, their relative stabilities, and to predict their infrared spectra. Comparisons of the measured IRMPD and predicted IR spectra elucidate the structures contributing to the experimental spectra. Coexistence of two modes of binding of Lys to Pt is found where Lys binds via the backbone and side-chain amino nitrogen atoms, NN s , or to the backbone amino and carboxylate oxygen atoms, NO - . Glycine-linked cisplatin and arginine-linked cisplatin complexes have previously been found to bind only via the NO - binding mode. Present results suggest that the NN s binding conformers may be key to the outstanding reactivity of Lysplatin toward DNA and RNA. |
