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