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

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.

SUBMITTER: Fete MG

PROVIDER: S-EPMC6664274 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Fete Matthew G MG Betker Jamie L JL Shoemaker Richard K RK Anchordoquy Thomas J TJ

Therapeutic delivery 20190101 1

<h4>Aim</h4>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.<h4>Materials & methods</h4>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.< ...[more]

PMID: 30730822

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