| Autor: |
Les P, Miranda, Licheng, Shi, Jerry R, Holder, Marie, Wright, Colin V, Gegg, Eileen, Johnson, Kenneth, Wild, Michael, Stenkilsson, George, Doellgast, Barton H, Manning, Kevin, Salyers |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Biopolymers. 100(4) |
| ISSN: |
1097-0282 |
| Popis: |
Antagonism of the calcitonin gene-related peptide (CGRP) receptor may be a useful approach for migraine treatment. Selective PEGylated peptide antagonists to the CGRP receptor are described, derived from CGRP(8-37) with polymer derivatization at an engineered lysine-25 residue. Potent PEGylated peptides with improved pharmacokinetics were identified through peptide side-chain modification to mitigate metabolic liabilities. PEGylated Ac-Trp-[Cit(11,18),hArg(24),Lys(25),Asp(31),Pro(34),1-Nal(35)]CGRP(8-37)-NH2, 9, elicits a dose-dependent reduction of intradermal CGRP-induced local blood flow in rodents with an ED50 of 0.52 mg kg(-1) without any overt adverse effects. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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