Abstract:
: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.
journal_name
Biopolymersjournal_title
Biopolymersauthors
Miranda LP,Shi L,Holder JR,Wright M,Gegg CV,Johnson E,Wild K,Stenkilsson M,Doellgast G,Manning BH,Salyers Kdoi
10.1002/bip.22270subject
Has Abstractpub_date
2013-07-01 00:00:00pages
422-30issue
4eissn
0006-3525issn
1097-0282journal_volume
100pub_type
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