Structure of Human Phosphodiesterase 5A1 Complexed with Avanafil Reveals Molecular Basis of Isoform Selectivity and Guidelines for Targeting α-Helix Backbone Oxygen by Halogen Bonding.
J Med Chem
; 63(15): 8485-8494, 2020 08 13.
Article
em En
| MEDLINE
| ID: mdl-32663396
ABSTRACT
Phosphodiesterase 5A1 (PDE5) is a key target for treating cardiovascular diseases and erectile dysfunction. Here, we report the crystal structure of PDE5 complexed with the sole second generation drug avanafil. Analysis of protein-drug interactions revealed the structural basis of avanafil's superior isoform selectivity. Moreover, a halogen bonding was observed between avanafil and a backbone carbonyl oxygen of an adjacent α-helix, whose contribution to inhibitory potency illustrates the feasibility of exploiting α-helix backbone in structure-based drug design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
/
Inibidores da Fosfodiesterase 5
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article