Computationally designed peptide inhibitors of the ubiquitin E3 ligase SCF(Fbx4)

Chembiochem. 2013 Mar 4;14(4):445-51. doi: 10.1002/cbic.201200777. Epub 2013 Feb 11.

Abstract

A structure-based computational approach was used to rationally design peptide inhibitors that can target an E3 ligase (SCF(Fbx4) )-substrate (TRF1) interface and subsequent ubiquitylation. Characterization of the inhibitors demonstrates that our sequence-optimization protocol results in an increase in peptide-TRF1 affinity without compromising peptide-protein specificity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Drug Design
  • F-Box Proteins / antagonists & inhibitors*
  • F-Box Proteins / chemistry
  • F-Box Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / pharmacology*
  • Protein Binding / drug effects*
  • Protein Interaction Maps / drug effects
  • Telomeric Repeat Binding Protein 1 / antagonists & inhibitors
  • Telomeric Repeat Binding Protein 1 / chemistry
  • Telomeric Repeat Binding Protein 1 / metabolism
  • Ubiquitination / drug effects

Substances

  • F-Box Proteins
  • FBXO4 protein, human
  • Peptides
  • Telomeric Repeat Binding Protein 1