期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 629, 期 -, 页码 95-100出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.09.007
关键词
Subtilase cytotoxin (SubAB); Shiga-toxigenic Escherichia coli (STEC); Multivalent peptide library screening; SubAB absorber
资金
- Research Program on Emerging and Re-emerging Infectious Diseases from the Japan Agency for Medical Research and Development (AMED) [JP18fk0108065, JP21fk0108611h0601, 21fk0108611h0701]
A series of multivalent peptides that efficiently bind to the receptor-binding region of SubAB were identified, and these peptides competitively inhibited the binding of SubAB to receptor molecules. One specific peptide, FFP-tet, was able to absorb SubAB cytotoxicity through direct binding to the toxin. These findings suggest that FFP-tet-beads may be an effective therapeutic agent for complications arising from eae-negative STEC infection.
Subtilase cytotoxin (SubAB) is a major virulence factor produced by eae-negative Shiga-toxigenic Escherichia coli (STEC) that can cause fatal systemic complications. SubAB binds to target cells through multivalent interactions between its B-subunit pentamer and receptor molecules such as glycoproteins with a terminal N-glycolylneuraminic acid (Neu5Gc). We screened randomized multivalent peptide li-braries synthesized on a cellulose membrane and identified a series of tetravalent peptides that effi-ciently bind to the receptor-binding region of the SubAB B-subunit pentamer. These peptides competitively inhibited the binding of the B-subunit to a receptor-mimic molecule containing clustered Neu5Gc (Neu5Gc-polymer). We selected the peptide with the highest inhibitory efficacy, FFP-tet, and covalently bound it to beads to synthesize FFP-tet-beads, a highly clustered SubAB absorber that dis-played potency to absorb SubAB cytotoxicity through direct binding to the toxin. The efficacy of FFP-tet-beads to absorb SubAB cytotoxicity in solution was similar to that of Neu5Gc-polymer, suggesting that FFP-tet-beads might be an effective therapeutic agent against complications arising from eae-negative STEC infection.(c) 2022 Elsevier Inc. All rights reserved.
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