Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein–protein interactions

Joel A. Drewry; Steven Fletcher; Peibin Yue; Denys Marushchak; Wei Zhao; Sumaiya Sharmeen; Xiaolei Zhang; Aaron D. Schimmer; Claudiu Gradinaru; James Turkson; Patrick T. Gunning

doi:10.1039/B919608K

Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein–protein interactions†

Joel A. Drewry,^ab Steven Fletcher,^ab Peibin Yue,^c Denys Marushchak,^b Wei Zhao,^c Sumaiya Sharmeen,^d Xiaolei Zhang,^c Aaron D. Schimmer,^d Claudiu Gradinaru,^b James Turkson^c and Patrick T. Gunning*^ab

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* Corresponding authors

^a Department of Chemistry, University of Toronto, Toronto, Canada
E-mail: patrick.gunning@utoronto.ca

^b Department of Chemical & Physical Sciences, 3359 Mississauga Rd. N., Mississauga, Canada
Fax: +1 905-569-4929
Tel: +1 905-569-4588

^c Department of Molecular Biology and Microbiology, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, USA

^d Ontario Cancer Institute/Princess Margaret Hospital, 610 University Avenue, Toronto, Canada

Abstract

We report the first application of coordination complexes as functional proteomimetics of the Src homology 2 (SH2) phosphopeptide-binding domain. As a proof-of-concept, functionalized bis-dipicolylamine (BDPA) copper(II) complexes are shown to disrupt oncogenic Stat3–Stat3 protein complexes and elicit promising anti-tumour activity.

Chemical Communications

Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein–protein interactions†

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Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein–protein interactions

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