Solid-Phase Thiol-Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist.
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.
['Williams|Elyse T|ET|', 'Harris|Paul W R|PWR|', 'Jamaluddin|Muhammad A|MA|', 'Loomes|Kerry M|KM|', 'Hay|Debbie L|DL|', 'Brimble|Margaret A|MA|0000-0002-7086-4096']
D000595:Amino Acid Sequence D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists D003545:Cysteine D008055:Lipids D010455:Peptides D060327:Solid-Phase Synthesis Techniques D013237:Stereoisomerism
lipidation peptides conjugation solid-phase synthesis synthetic methods