We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Solid‐Phase Thiol–Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist.
- Authors
Williams, Elyse T.; Harris, Paul W. R.; Jamaluddin, Muhammad A.; Loomes, Kerry M.; Hay, Debbie L.; Brimble, Margaret A.
- Abstract
Abstract: We report a new method herein coined SP‐CLipPA (solid‐phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono‐S‐lipidated peptides. This technique utilizes thiol–ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin‐bound peptide. Advantages of SP‐CLipPA include: ease of handling, conversions of up to 91 %, by‐product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP‐HPLC purification. To showcase the utility of SP‐CLipPA, we synthesized a potent calcitonin gene‐related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP8–37 and CGRP7–37, has potential for the treatment of migraine.
- Subjects
PEPTIDES; AMINO acids; THIOLS; THIOL synthesis; VINYL ester resins; CALCITONIN
- Publication
Angewandte Chemie, 2018, Vol 130, Issue 36, p11814
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201805208