Novel Macrocyclic Antagonists of the Calcitonin Gene-Related Peptide Receptor: Design, Realization, and Structural Characterization of Protein-Ligand Complexes.
ACS Chem Neurosci
; 13(6): 751-765, 2022 03 16.
Article
em En
| MEDLINE
| ID: mdl-35245037
ABSTRACT
A series of macrocyclic calcitonin gene-related peptide (CGRP) receptor antagonists identified using structure-based design principles, exemplified by HTL0028016 (1) and HTL0028125 (2), is described. Structural characterization by X-ray crystallography of the interaction of two of the macrocycle antagonists with the CGRP receptor ectodomain is described, along with structure-activity relationships associated with point changes to the macrocyclic antagonists. The identification of non-peptidic/natural product-derived, macrocyclic ligands for a G protein coupled receptor (GPCR) is noteworthy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Peptídeo Relacionado com o Gene de Calcitonina
/
Receptores Acoplados a Proteínas G
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article