Genetically Encoded Cholesterol-Modified Polypeptides
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 PT...
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Published in | Journal of the American Chemical Society Vol. 141; no. 2; pp. 945 - 951 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
16.01.2019
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Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author Contributions Current Address: Department of Chemistry, Syracuse University, Center for Science and Technology, 111 College Place, Syracuse, NY, 13244. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. |
ISSN: | 0002-7863 1520-5126 |
DOI: | 10.1021/jacs.8b10687 |