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Examination of ?-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid.

ABSTRACT: Botulinum neurotoxins (BoNT) are among the most toxic known substances and currently there are no effective treatments for intraneuronal BoNT intoxication. Chicoric acid (ChA) was previously reported as a BoNT/A inhibitor that binds to the enzyme's ?-exosite. Herein, we report the synthesis and structure-activity relationships (SARs) of a series of ChA derivatives, which revealed essential binding interactions between ChA and BoNT/A. Moreover, several ChA-based inhibitors with improved potency against the BoNT/A were discovered.

SUBMITTER: Xue S

PROVIDER: S-EPMC5667901 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Examination of α-exosite inhibitors against Botulinum neurotoxin A protease through structure-activity relationship studies of chicoric acid.

Xue Song S Seki Hajime H Remes Marek M Šilhár Peter P Janda Kim K

Bioorganic & medicinal chemistry letters 20171012 22

Botulinum neurotoxins (BoNT) are among the most toxic known substances and currently there are no effective treatments for intraneuronal BoNT intoxication. Chicoric acid (ChA) was previously reported as a BoNT/A inhibitor that binds to the enzyme's α-exosite. Herein, we report the synthesis and structure-activity relationships (SARs) of a series of ChA derivatives, which revealed essential binding interactions between ChA and BoNT/A. Moreover, several ChA-based inhibitors with improved potency a ...[more]

PMID: 29050781

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Botulinum neurotoxin A protease: discovery of natural product exosite inhibitors.

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Tyrosine phosphorylation of botulinum neurotoxin protease domains.

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Identification of a Natural Product Antagonist against the Botulinum Neurotoxin Light Chain Protease.

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