Alteration of cytosine-guanine interactions due to N7 metal cation binding: a structure-activity relationship for cisplatin analogues
Barnett, G.
Molecular Pharmacology 29(4): 378-382
1986
ISSN/ISBN: 0026-895X PMID: 3702856 Document Number: 282737
Metal cation binding to N7 of guanine (G) and the resulting altered interaction with cytosine (C) were investigated by ab initio quantum chemical calculations for the ions Li+, Na+, B+, Be2+, and Mg2+. It was found that the CG H-bonding interaction becomes more stable and the stacking interaction less stable as the charge density for the ion (ion charge/ionic radius) increases. From this observation a hypothesis is presented for a structure-activity relationship, which is supported by in vivo animal data, that may permit the design of less toxic analogues of the antitumor agent cisplatin.