Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides.
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Tan, Yaw Sing
Abstract
Herein, we describe the development of a novel staple with an electrophilic warhead to enable the generation of stapled peptide covalent inhibitors of the p53-MDM2 protein-protein interaction (PPI). The peptide developed showed complete and selective covalent binding resulting in potent inhibition of p53-MDM2 PPI.
Description
Keywords
Binding Sites, Enzyme Inhibitors, Humans, Lysine, Molecular Dynamics Simulation, Muramidase, Peptides, Cyclic, Proto-Oncogene Proteins c-mdm2, Saccharomyces cerevisiae, Sulfones
Journal Title
Chem Commun (Camb)
Conference Name
Journal ISSN
1359-7345
1364-548X
1364-548X
Volume Title
55
Publisher
Royal Society of Chemistry (RSC)
Publisher DOI
Rights
All rights reserved
Sponsorship
Engineering and Physical Sciences Research Council (EP/J016012/1)
Engineering and Physical Sciences Research Council (EP/P020291/1)
Engineering and Physical Sciences Research Council (1800602)
Engineering and Physical Sciences Research Council (EP/P020291/1)
Engineering and Physical Sciences Research Council (1800602)
Royal Society, Trinity College, A*STAR (IAF-PP H17/01/a0/010)