Lipidated Stapled Peptides Targeting the Acyl Binding Protein UNC119

Chembiochem. 2019 Dec 13;20(24):2987-2990. doi: 10.1002/cbic.201900615. Epub 2019 Nov 19.

Abstract

The acyl-binding UNC119 proteins mediate the activation and transport of various N-myristoylated proteins. In particular, UNC119a plays a crucial role in the completion of cytokinesis. Herein, we report the use of a lipidated peptide originating from the UNC119 binding partner Gnat1 as the basis for the design of lipidated, stabilized α-helical peptides that target UNC119a. By using the hydrocarbon peptide-stapling approach, cell-permeable binders of UNC119a were generated that induced the accumulation of cytokinetic and binucleated cells; this suggests UNC119a as a potential target for the inhibition of cytokinesis.

Keywords: alpha-helixes; macrocyclization; peptidomimetics; protein-protein interaction; trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • HeLa Cells
  • Humans
  • Lipid Metabolism*
  • Models, Molecular
  • Molecular Targeted Therapy
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptides / pharmacology*
  • Protein Binding
  • Protein Conformation, alpha-Helical

Substances

  • Adaptor Proteins, Signal Transducing
  • Peptides
  • UNC119 protein, human