ArticleProceedings of the National Academy of Sciences of the United States of America2014
Design of ultrasensitive probes for human neutrophil elastase through hybrid combinatorial substrate library profiling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed.
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Two Shorter Variants of the Proline-Rich Antimicrobial Peptide B7-005 Scaffold Active Against Clinical Isolates ofAntibiotics (Basel, Switzerland) · 2026Article
- Chemical probes for enzyme imaging: challenges in design, synthesis and biomedical applications.Chemical science · 2025Review
- Identifying protease-activated targets and exploring therapeutic applications.Expert opinion on therapeutic targets · 2025Review
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Nanobody-Targeted Conditional Antimicrobial Therapeutics.ACS nano · 2025Article
- A breath-based in vitro diagnostic assay for the detection of lower respiratory tract infections.PNAS nexus · 2024Article
- Human Neutrophil Elastase: Characterization of Intra- vs. Extracellular Inhibition.International journal of molecular sciences · 2024Article
- Label-free detection of biomolecules using inductively coupled plasma mass spectrometry (ICP-MS).Analytical and bioanalytical chemistry · 2024Review
- Targeted Library of Phosphonic-Type Inhibitors of Human Neutrophil Elastase.Molecules (Basel, Switzerland) · 2024Article
- Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023Review
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- Fluorescent Activity-Based Probe To Image and Inhibit Factor XIa Activity in Human Plasma.Journal of medicinal chemistry · 2023Article
- Evaluation of variable new antigen receptors (vNARs) as a novel cathepsin S (CTSS) targeting strategy.Frontiers in pharmacology · 2023Article
- A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell Invasion.Journal of the American Chemical Society · 2022Article
- Peptidyl-Resin Substrates as a Tool in the Analysis of Caspase Activity.Molecules (Basel, Switzerland) · 2022Article
- Host protease activity classifies pneumonia etiology.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Parallel imaging of coagulation pathway proteases activated protein C, thrombin, and factor Xa in human plasma.Chemical science · 2022Article
- Development of a fluorescent probe library enabling efficient screening of tumour-imaging probes based on discovery of biomarker enzymatic activities.Chemical science · 2022Article
- Sequence preference and scaffolding requirement for the inhibition of human neutrophil elastase by ecotin peptide.Protein science : a publication of the Protein Society · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
The exploration of protease substrate specificity is generally restricted to naturally occurring amino acids, limiting the degree of conformational space that can be surveyed. We substantially enhanced this by incorporating 102 unnatural amino acids to explore the S1-S4 pockets of human neutrophil elastase. This approach provides hybrid natural and unnatural amino acid sequences, and thus we termed it the Hybrid Combinatorial Substrate Library. Library results were validated by the synthesis of individual tetrapeptide substrates, with the optimal substrate demonstrating more than three orders of magnitude higher catalytic efficiency than commonly used substrates of elastase. This optimal substrate was converted to an activity-based probe that demonstrated high selectivity and revealed the specific presence of active elastase during the process of neutrophil extracellular trap formation. We propose that this approach can be successfully used for any type of endopeptidase to deliver high activity and selectivity in substrates and probes.
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