Genetically Encoded Cholesterol-Modified Polypeptides.

Journal Article (Journal Article)

Biological systems use post-translational modifications (PTMs) to control the structure, location, and function of proteins after expression. Despite the ubiquity of PTMs in biology, their use to create genetically encoded recombinant biomaterials is limited. We have utilized a natural lipidation PTM (hedgehog-mediated cholesterol modification of proteins) to create a class of hybrid biomaterials called cholesterol-modified polypeptides (CHaMPs) that exhibit programmable self-assembly at the nanoscale. To demonstrate the biomedical utility of CHaMPs, we used this approach to append cholesterol to biologically active peptide exendin-4 that is an approved drug for the treatment of type II diabetes. The exendin-cholesterol conjugate self-assembled into micelles, and these micelles activate the glucagon-like peptide-1 receptor with a potency comparable to that of current gold standard treatments.

Full Text

Duke Authors

Cited Authors

  • Mozhdehi, D; Luginbuhl, KM; Dzuricky, M; Costa, SA; Xiong, S; Huang, FC; Lewis, MM; Zelenetz, SR; Colby, CD; Chilkoti, A

Published Date

  • January 4, 2019

Published In

Volume / Issue

  • 141 / 2

Start / End Page

  • 945 - 951

PubMed ID

  • 30608674

Pubmed Central ID

  • PMC6693588

Electronic International Standard Serial Number (EISSN)

  • 1520-5126

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/jacs.8b10687


  • eng