A genetically selected cyclic peptide inhibitor of BCL6 homodimerization

Eliot L Osher; Francisco Castillo; Nagarajan Elumalai; Michael J Waring; Garry Pairaudeau; Ali Tavassoli

doi:10.1016/j.bmc.2018.03.012

A genetically selected cyclic peptide inhibitor of BCL6 homodimerization

Bioorg Med Chem. 2018 Jul 15;26(11):3034-3038. doi: 10.1016/j.bmc.2018.03.012. Epub 2018 Mar 9.

Authors

Eliot L Osher¹, Francisco Castillo¹, Nagarajan Elumalai¹, Michael J Waring², Garry Pairaudeau³, Ali Tavassoli⁴

Affiliations

¹ Chemistry, University of Southampton, Southampton SO17 1BJ, UK.
² Northern Institute for Cancer Research, Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
³ AstraZeneca, Cambridge Science Park, 310 Milton Rd. Cambridge CB40FZ, UK.
⁴ Chemistry, University of Southampton, Southampton SO17 1BJ, UK. Electronic address: a.tavassoli@soton.ac.uk.

PMID: 29555420
DOI: 10.1016/j.bmc.2018.03.012

Abstract

We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its homodimerization, and subsequent binding of the SMRT2 corepressor peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dimerization
Gene Library*
Molecular Structure
Peptides, Cyclic / chemistry
Peptides, Cyclic / genetics
Peptides, Cyclic / pharmacology*
Protein Binding
Proto-Oncogene Proteins c-bcl-6 / antagonists & inhibitors*
Proto-Oncogene Proteins c-bcl-6 / genetics

Substances

BCL6 protein, human
Peptides, Cyclic
Proto-Oncogene Proteins c-bcl-6