Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/55481
Title: Substrate-based inhibitors exhibiting excellent protective and therapeutic effects against botulinum neurotoxin a intoxication
Authors: Guo, J
Wang, J
Gao, S
Ji, B
Chan, WCE
Chen, S 
Issue Date: 2015
Publisher: Nature Publishing Group
Source: Scientific reports, 2015, v. 5, 16981 How to cite?
Journal: Scientific reports 
Abstract: Potent inhibitors to reverse Botulinum neurotoxins (BoNTs) activity in neuronal cells are currently not available. A better understanding of the substrate recognition mechanism of BoNTs enabled us to design a novel class of peptide inhibitors which were derivatives of the BoNT/A substrate, SNAP25. Through a combination of in vitro, cellular based, and in vivo mouse assays, several potent inhibitors of approximately one nanomolar inhibitory strength both in vitro and in vivo have been identified. These compounds represent the first set of inhibitors that exhibited full protection against BoNT/A intoxication in mice model with undetectable toxicity. Our findings validated the hypothesis that a peptide inhibitor targeting the two BoNT structural regions which were responsible for substrate recognition and cleavage respectively could exhibit excellent inhibitory effect, thereby providing insight on future development of more potent inhibitors against BoNTs.
URI: http://hdl.handle.net/10397/55481
EISSN: 2045-2322
DOI: 10.1038/srep16981
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