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In Silico Peptide-Directed Ligand Design Complements Experimental Peptide-Directed Binding for Protein-Protein Interaction Modulator Discovery

preprint
submitted on 21.06.2020 and posted on 24.06.2020 by Lesley A. Howell, Andrew Beekman
Using the protein-protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80%. The two rapid and efficient methods demonstrate complementary features for protein-protein interaction modulator discovery.

Funding

RGS\R1\201008

Combining Click Chemistry & Peptide Synthesis to Generate Novel Inhibitors of the Anti-Apoptotic Protein Mcl-1 for the Treatment of Pancreatic Cancer

Engineering and Physical Sciences Research Council

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History

Email Address of Submitting Author

a.beekman@uea.ac.uk

Institution

University of East Anglia

Country

United Kingdom

ORCID For Submitting Author

0000-0002-3056-6406

Declaration of Conflict of Interest

No conflict of Interest

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