A novel method for conjugating the terminal amine of peptide ligands to cholesterol: synthesis iRGD-cholesterol. (7th December 2018)

• Record Type: Journal Article
• Authors: Fete, Matthew G; Betker, Jamie L; Shoemaker, Richard K; Anchordoquy, Thomas J
• Is Part Of: Therapeutic delivery. Volume 10:Number 1(2019)
• Page Start: 11
• Page End: 20
• Publication Date: 2018-12-07
• Subjects: nanotechnology -- oligonucleotides -- targeting – cellular; Drug delivery systems -- Periodicals; Therapeutics -- Periodicals; 615.6
• DOI: 10.4155/tde-2018-0057
• Languages: English
• ISSNs: 2041-5990

Abstract

Aim: 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.Materials & methods: 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.Results & conclusion: 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.