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A novel method for conjugating the terminal amine of peptide ligands to cholesterol: synthesis iRGD-cholesterol.

Authors
  • Fete, Matthew G1
  • Betker, Jamie L2
  • Shoemaker, Richard K3
  • Anchordoquy, Thomas J2
  • 1 School of Pharmacy, Rueckert-Hartman College, Regis University, 3333 Regis Blvd, Denver, CO 80221 USA.
  • 2 Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd, Aurora, CO 80045 USA.
  • 3 Department of Chemistry & Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
Type
Published Article
Journal
Therapeutic Delivery
Publisher
"Future Science, LTD"
Publication Date
Jan 01, 2019
Volume
10
Issue
1
Pages
11–20
Identifiers
DOI: 10.4155/tde-2018-0057
PMID: 30730822
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Conventional conjugation reactions often involve the use of activated PEG as a linker, but concerns about PEG-mediated reduction in intracellular delivery and enhanced immunogenicity have generated interest in developing methods that eliminate the need for a PEG linker. Reaction conditions were identified that specifically couples the terminal amine of a cyclic iRGD peptide (CRGDRGPDC) to the hydroxyl moiety of cholesterol through a short carbamate linker. Using this method for synthesizing iRGD-cholesterol, peptide ligands can be incorporated into lipid-based delivery systems, thereby eliminating concerns about adverse reactions to PEG. Toxicity and stability data indicate low toxicity and adequate serum stability at low ligand levels.

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