ArticleAngewandte Chemie (International ed. in English)2015
Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.
Article in Angewandte Chemie (International ed. in English), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Click Reactions in Kinetic Target-Guided Synthesis: Progress in the Discovery of Inhibitors for Biological Targets.Methods and protocols · 2026Review
- A novel RRGW derived peptide is a promising inhibitor of BoNT/A.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions.Communications chemistry · 2023Article
- Facile de Novo Sequencing of Tetrazine-Cyclized Peptides through UV-Induced Ring-Opening and Cleavage from the Solid Phase.Chembiochem : a European journal of chemical biology · 2023Article
- Protein Catalyzed Capture (PCC) Agents for Antigen Targeting.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Copper-ligand clusters dictate size of cyclized peptide formed during alkyne-azide cycloaddition on solid support.RSC advances · 2021Article
- Article
- Protein-Catalyzed Capture Agents.Chemical reviews · 2019Review
- Chemical composition of DNA-encoded libraries, past present and future.Organic & biomolecular chemistry · 2019Review
- Ribosome-Templated Azide-Alkyne Cycloadditions Using Resistant Bacteria as Reaction Vessels:ACS medicinal chemistry letters · 2018Article
- Allosteric Inhibitor of KRas Identified Using a Barcoded Assay Microchip Platform.Analytical chemistry · 2018Article
- Degradation of Akt using protein-catalyzed capture agents.Journal of peptide science : an official publication of the European Peptide Society · 2016Article
- A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.Angewandte Chemie (International ed. in English) · 2015Article
- Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.PloS one · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.