Journal:JBSD:32

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Cooperative Stabilization of Zn2+: DNA Complexes Through Netropsin Binding in the Minor Groove of FdU-Substituted DNA

Supratim Ghosh, Freddie R. Salsbury Jr., David A. Horita and William H. Gmeiner [1]


Molecular Tour
We find that a hairpin DNA that incorporates the modified base FdU when complexed with the small molecule netropsin and zinc displays increased cytotoxicity towards PC3 prostate cancer cells relatives to their components or separate complexes. In order to investigate the origin of this cytotoxicity, we used NMR spectroscopy, circular dichroism, and semi-empirical quantum mechanical calculations to study and model the new structural motif formed by this complex. In this complex, the netropsin binds to the minor groove whereas zinc binds to the major groove simultaneously.

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  1. Ghosh S, Salsbury FR Jr, Horita DA, Gmeiner WH. Cooperative stabilization of Zn(2+):DNA complexes through netropsin binding in the minor groove of FdU-substituted DNA. J Biomol Struct Dyn. 2012 Nov 16. PMID:23153072 doi:10.1080/07391102.2012.732343

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