Genetically Encoded Cholesterol-Modified Polypeptides

Davoud Mozhdehi, Kelli M. Luginbuhl, Michael Dzuricky, Simone A. Costa, Sinan Xiong, Fred C. Huang, Mae M. Lewis, Stephanie R. Zelenetz, Christian D. Colby, Ashutosh Chilkoti

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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. ©

Original languageEnglish (US)
Pages (from-to)945-951
Number of pages7
JournalJournal of the American Chemical Society
Volume141
Issue number2
DOIs
StatePublished - Jan 16 2019

Fingerprint

Polypeptides
Cholesterol
Biocompatible Materials
Post Translational Protein Processing
Peptides
Biomaterials
Micelles
Proteins
Biological systems
Medical problems
Self assembly
Type 2 Diabetes Mellitus
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Mozhdehi, D., Luginbuhl, K. M., Dzuricky, M., Costa, S. A., Xiong, S., Huang, F. C., ... Chilkoti, A. (2019). Genetically Encoded Cholesterol-Modified Polypeptides. Journal of the American Chemical Society, 141(2), 945-951. https://doi.org/10.1021/jacs.8b10687

Genetically Encoded Cholesterol-Modified Polypeptides. / Mozhdehi, Davoud; Luginbuhl, Kelli M.; Dzuricky, Michael; Costa, Simone A.; Xiong, Sinan; Huang, Fred C.; Lewis, Mae M.; Zelenetz, Stephanie R.; Colby, Christian D.; Chilkoti, Ashutosh.

In: Journal of the American Chemical Society, Vol. 141, No. 2, 16.01.2019, p. 945-951.

Research output: Contribution to journalArticle

Mozhdehi, D, Luginbuhl, KM, Dzuricky, M, Costa, SA, Xiong, S, Huang, FC, Lewis, MM, Zelenetz, SR, Colby, CD & Chilkoti, A 2019, 'Genetically Encoded Cholesterol-Modified Polypeptides', Journal of the American Chemical Society, vol. 141, no. 2, pp. 945-951. https://doi.org/10.1021/jacs.8b10687
Mozhdehi D, Luginbuhl KM, Dzuricky M, Costa SA, Xiong S, Huang FC et al. Genetically Encoded Cholesterol-Modified Polypeptides. Journal of the American Chemical Society. 2019 Jan 16;141(2):945-951. https://doi.org/10.1021/jacs.8b10687
Mozhdehi, Davoud ; Luginbuhl, Kelli M. ; Dzuricky, Michael ; Costa, Simone A. ; Xiong, Sinan ; Huang, Fred C. ; Lewis, Mae M. ; Zelenetz, Stephanie R. ; Colby, Christian D. ; Chilkoti, Ashutosh. / Genetically Encoded Cholesterol-Modified Polypeptides. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 2. pp. 945-951.
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