Structure-Based Design, Synthesis and Bioactivity of a New Anti-TNFα Cyclopeptide.
Molecules
; 25(4)2020 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-32093030
ABSTRACT
As opposed to small molecules, macrocyclic peptides possess a large surface area and are recognised as promising candidates to selectively treat diseases by disrupting specific protein-protein interactions (PPIs). Due to the difficulty in predicting cyclopeptide conformations in solution, the de novo design of bioactive cyclopeptides remains significantly challenging. In this study, we used the combination of conformational analyses and molecular docking studies to design a new cyclopeptide inhibitor of the interaction between the human tumour necrosis factor alpha (TNFα) and its receptor TNFR-1. This interaction is a key in mediating the inflammatory response to tissue injury and infection in humans, and it is also an important causative factor of rheumatoid arthritis, psoriasis and inflammatory bowel disease. The solution state NMR structure of the cyclopeptide was determined, which helped to deduce its mode of interaction with TNFα. TNFα sensor cells were used to evaluate the biological activity of the peptide.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Desenho de Fármacos
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Fator de Necrose Tumoral alfa
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Molecules
Ano de publicação:
2020
Tipo de documento:
Article