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Title: Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells
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 Pep tide B inding D esign (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin 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 K D of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).  more » « less
Award ID(s):
1934284
PAR ID:
10465235
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Communications Biology
Volume:
6
Issue:
1
ISSN:
2399-3642
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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