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Genetically Encoded Cholesterol-Modified Polypeptides.

Publication ,  Journal Article
Mozhdehi, D; Luginbuhl, KM; Dzuricky, M; Costa, SA; Xiong, S; Huang, FC; Lewis, MM; Zelenetz, SR; Colby, CD; Chilkoti, A
Published in: Journal of the American Chemical Society
January 2019

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.

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Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

January 2019

Volume

141

Issue

2

Start / End Page

945 / 951

Related Subject Headings

  • Protein Processing, Post-Translational
  • Protein Engineering
  • Proof of Concept Study
  • Micelles
  • Humans
  • HEK293 Cells
  • Glucagon-Like Peptide-1 Receptor
  • General Chemistry
  • Exenatide
  • Escherichia coli
 

Citation

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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
Mozhdehi, Davoud, Kelli M. Luginbuhl, Michael Dzuricky, Simone A. Costa, Sinan Xiong, Fred C. Huang, Mae M. Lewis, Stephanie R. Zelenetz, Christian D. Colby, and Ashutosh Chilkoti. “Genetically Encoded Cholesterol-Modified Polypeptides.Journal of the American Chemical Society 141, no. 2 (January 2019): 945–51. 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;141(2):945–51.
Mozhdehi, Davoud, et al. “Genetically Encoded Cholesterol-Modified Polypeptides.Journal of the American Chemical Society, vol. 141, no. 2, Jan. 2019, pp. 945–51. Epmc, doi:10.1021/jacs.8b10687.
Mozhdehi D, Luginbuhl KM, Dzuricky M, Costa SA, Xiong S, Huang FC, Lewis MM, Zelenetz SR, Colby CD, Chilkoti A. Genetically Encoded Cholesterol-Modified Polypeptides. Journal of the American Chemical Society. 2019 Jan;141(2):945–951.
Journal cover image

Published In

Journal of the American Chemical Society

DOI

EISSN

1520-5126

ISSN

0002-7863

Publication Date

January 2019

Volume

141

Issue

2

Start / End Page

945 / 951

Related Subject Headings

  • Protein Processing, Post-Translational
  • Protein Engineering
  • Proof of Concept Study
  • Micelles
  • Humans
  • HEK293 Cells
  • Glucagon-Like Peptide-1 Receptor
  • General Chemistry
  • Exenatide
  • Escherichia coli