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International Journal of Inorganic Chemistry
Volume 2011 (2011), Article ID 319757, 17 pages
http://dx.doi.org/10.1155/2011/319757
Research Article

Insights into DNA Platination within Unusual Structural Settings

WestCHEM Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK

Received 15 September 2011; Accepted 24 November 2011

Academic Editor: Stephen Ralph

Copyright © 2011 Stephanie Harvie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

2D [ 1 H , 1 5 N ] HSQC NMR spectroscopy has been used to monitor reaction and product formation between [ P t ( 1 5 N H 3 ) 2 I 2 ] and nucleic acids possessing irregular topologies and containing site-specific phosphorothioate substitution in the phosphodiester backbone. Comparison of the reaction profiles of dimer nucleic acids with and without phosphorothioate substitution is made with their short nucleic acid counterparts containing the key dimer components. Whereas d(GpA) is relatively unreactive towards [ P t ( 1 5 N H 3 ) 2 I 2 ] , NMR evidence suggests that the tandem sheared mismatch duplex d(GCG3pAGC)2 reacts to form the head-to-tail interstrand G3-N7-Pt-G3-N7 cross-link. The equivalent phosphorothioate R,S-d(GsA) reacts to form a monoiodo, monosulphur adduct, whereas the tandem sheared mismatch phosphorothioate duplex d(GCGsAG5C)2 (VIs) reacts to form the unusual intrastrand macrochelate [ P t ( 1 5 N H 3 ) 2 { d ( V I s - G 5 - 𝑁 7 ) } , 𝑆 ] 2 + , in which platinum is attached at both sulphur and G5-N7. Experimental evidence supports the formation of a stabilized mismatch duplex in which platinum is attached to two nitrogen centres in the sequence d(CGCGpTGCG) in contrast to R,S-d(CGCGsT5GCG) for which NMR evidence supports macrochelate-stabilized hairpin loop formation cross-linked at both phosphorothioate sulphur and T5-N3.