Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells.
Commun Biol
; 6(1): 878, 2023 08 26.
Article
em En
| MEDLINE
| ID: mdl-37634026
ABSTRACT
Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity of these toxins represent a promising therapeutic strategy to prevent and treat C. diff. infection. We describe an approach that combines a Peptide Binding Design (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptidetoxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in colon epithelial cells. One peptide, SA1, is found to block TcdA toxicity in primary-derived human colon (large intestinal) epithelial cells. SA1 binds TcdA with a KD of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clostridioides difficile
Limite:
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos