Matthew G Fete1, Jamie L Betker2, Richard K Shoemaker3, Thomas J Anchordoquy2. 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.
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.
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.
Authors: A Santel; M Aleku; O Keil; J Endruschat; V Esche; G Fisch; S Dames; K Löffler; M Fechtner; W Arnold; K Giese; A Klippel; J Kaufmann Journal: Gene Ther Date: 2006-04-20 Impact factor: 5.250