Peptide antagonists of the calcitonin gene-related peptide (CGRP) receptor with improved pharmacokinetics and pharmacodynamics.
Biopolymers
; 100(4): 422-30, 2013 Jul.
Article
in En
| MEDLINE
| ID: mdl-23868210
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcitonin Gene-Related Peptide
/
Receptors, Calcitonin Gene-Related Peptide
Language:
En
Journal:
Biopolymers
Year:
2013
Document type:
Article