Asset Details
Do you wish to reserve the book?
Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment
Do you wish to request the book?
Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Pipeline for development of acylated peptide based CGRP receptor antagonist with extended half-life for migraine treatment
2025
Overview
Migraine is a debilitating headache disorder. The disease has neurovascular origin and migraine attacks can be elicited by vasodilative neuropeptides such as alpha calcitonin gene-related peptide (αCGRP). Antagonizing CGRP actions in migraine patients has proven clinically efficient. Here, we present a pipeline for development of a peptide-based hCGRP receptor antagonist with increased half-life capable of antagonising the vasodilatory effect of hαCGRP. A series of hαCGRP8-37 analogues carrying a C18-or C20-diacid lipidation was screened for their antagonism against the hCGRP receptor. hαCGRP8-37 analogues with a C20-diacid were 2-6 fold more potent than analogues conjugated with a C18-diacid. Half-life of hαCGRP8-37 analogues carrying a C20-diacid was estimated in mice in a pilot study (n = 1–2). Half-lives ranged from 7.3 to 13.7 h. An hαCGRP8-37 analogue conjugated with a C20 diacid at position 25 was subjected to an amino acid substitution scan to identify mutations that could further enhance hCGRP receptor antagonism. Substituting alanine with serine at position 36 resulted in a ~ 4 fold gain of potency. Vasodilative actions of hαCGRP were successfully antagonized by hαCGRP8-37 analogues carrying a C20 diacid at position 25. Our findings demonstrate that lipidation can improve hαCGRP8-37 pharmacokinetics while maintaining hαCGRP antagonism, thus demonstrating potential for a peptide-based migraine treatment strategy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/154
/ 631/45
/ Animals
/ Calcitonin gene-related peptide
/ Calcitonin Gene-Related Peptide - chemistry
/ Calcitonin Gene-Related Peptide - pharmacology
/ Calcitonin Gene-Related Peptide Receptor Antagonists - chemistry
/ Calcitonin Gene-Related Peptide Receptor Antagonists - pharmacokinetics
/ Calcitonin Gene-Related Peptide Receptor Antagonists - pharmacology
/ Calcitonin Gene-Related Peptide Receptor Antagonists - therapeutic use
/ Headache
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Migraine
/ Migraine Disorders - drug therapy
/ Migraine Disorders - metabolism
/ Peptides
/ Receptors, Calcitonin Gene-Related Peptide - metabolism
/ Science
