Design and synthesis of peptidic partial agonists of human neuromedin U receptor 1 with enhanced serum stability.
Bioorg Med Chem Lett
; 30(18): 127436, 2020 09 15.
Article
em En
| MEDLINE
| ID: mdl-32721452
ABSTRACT
Neuromedin U (NMU) activates two receptors (NMUR1 and NMUR2) and is a promising candidate for development of drugs to combat obesity. Previously, we obtained hexapeptides as selective full NMUR agonists. Development of a partial agonist which mildly activates receptors is an effective strategy which lead to an understanding of the functions of NMU receptors. In 2014, we reported hexapeptide 3 (CPN-124) as an NMUR1-selective partial agonist but its selectivity and serum stability were unsatisfactory. Herein, we report the development of a hexapeptide-type partial agonist (8, CPN-223) based on a peptide (3) but with higher NMUR1-selectivity and enhanced serum stability. A structure-activity relationship study of synthetic pentapeptide derivatives suggested that a hexapeptide is a minimum structure consistent with both good NMUR1-selective agonistic activity and serum stability.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Receptores de Neurotransmissores
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Fármacos Antiobesidade
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Obesidade
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article