A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display

Emil S. Iqbal; Stacie L. Richardson; Nicolas A. Abrigo; Kara K. Dods; H. Estheban Osorio Franco; Heather S. Gerrish; Hari Kiran Kotapati; Iain M. Morgan; Douglas S. Masterson; Matthew C. T. Hartman

doi:10.1039/C8CC10192B

A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display†

Emil S. Iqbal,

^ab Stacie L. Richardson,^ab Nicolas A. Abrigo,^ab Kara K. Dods,

^ab H. Estheban Osorio Franco,^ab Heather S. Gerrish,^ab Hari Kiran Kotapati,

^c Iain M. Morgan,^bd Douglas S. Masterson^c and Matthew C. T. Hartman

*^ab

Author affiliations

* Corresponding authors

^a Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, P. O. Box 842006, Richmond, VA 23284, USA
E-mail: mchartman@vcu.edu

^b Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Richmond, VA 23298, USA

^c School of Mathematics & Natural Sciences, Chemistry & Biochemistry, 118 College Drive #5043, Hattiesburg, MS 39406, USA

^d Philips Institute for Oral Health Research, Department of Oral and Craniofacial Molecular Biology, School of Dentistry, Virginia Commonwealth University, Box 980566, Richmond, VA 23298, USA

Abstract

Hydrocarbon stapled peptides are promising therapeutics for inhibition of intracellular protein–protein interactions. Here we develop a new high-throughput strategy for hydrocarbon stapled peptide discovery based on mRNA display of peptides containing α-methyl cysteine and cyclized with m-dibromoxylene. We focus on development of a peptide binder to the HPV16 E2 protein.

Chemical Communications

A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display†

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A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display

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