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A biomimetic approach for enhancing the in vivo half-life of peptides
Nature Chemical Biology
  • Sravan C. Penchala, University of the Pacific
  • Mark R. Miller, University of the Pacific
  • Arindom Pal, University of the Pacific
  • Jin Dong, University of the Pacific
  • Nikhil R. Madadi, University of the Pacific
  • Jinghang Xie, University of the Pacific
  • Hyun Joo, University of the Pacific
  • Jerry Tsai, University of the Pacific
  • Patrick Batoon, University of the Pacific
  • Vyacheslav V. Samoshin, University of the Pacific
  • Andreas H. Franz, University of the Pacific
  • Trevor Cox, University of the Pacific
  • Jesse Miles, University of the Pacific
  • William K. Chan, University of the Pacific
  • Miki S. Park, University of the Pacific
  • Mamoun M Alhamadsheh, University of the Pacific
Document Type
Article
Department
Chemistry
DOI
10.1038/nchembio.1907
Publication Date
9-7-2015
Disciplines
Abstract
The tremendous therapeutic potential of peptides has not yet been realized, mainly owing to their short in vivo half-life. Although conjugation to macromolecules has been a mainstay approach for enhancing protein half-life, the steric hindrance of macromolecules often harms the binding of peptides to target receptors, compromising the in vivo efficacy. Here we report a new strategy for enhancing the in vivo half-life of peptides without compromising their potency. Our approach involves endowing peptides with a small molecule that binds reversibly to the serum protein transthyretin. Although there are a few molecules that bind albumin reversibly, we are unaware of designed small molecules that reversibly bind other serum proteins and are used for half-life extension in vivo. We show here that our strategy was effective in enhancing the half-life of an agonist for GnRH receptor while maintaining its binding affinity, which was translated into superior in vivo efficacy.
Citation Information
Sravan C. Penchala, Mark R. Miller, Arindom Pal, Jin Dong, et al.. "A biomimetic approach for enhancing the in vivo half-life of peptides" Nature Chemical Biology Vol. 11 Iss. 10 (2015) p. 793 - 798 ISSN: 1552-4450
Available at: http://works.bepress.com/andreas-franz/57/