ArticlePloS one2013
Combinatorial optimization of cystine-knot peptides towards high-affinity inhibitors of human matriptase-1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- High-Throughput Activity Reprogramming of Proteases (HARP).ACS chemical biology · 2025Article
- Yeast as a tool for exploring disulfide-rich peptides.FEMS yeast research · 2025Review
- Ultra-High-Throughput Screening of Cystine-Rich Peptide Libraries Via Yeast Surface Display.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Plant peptides - redefining an area of ribosomally synthesized and post-translationally modified peptides.Natural product reports · 2024Review
- Lipidation of a bioactive cyclotide-based CXCR4 antagonist greatly improves its pharmacokinetic profile in vivo.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines.Plants (Basel, Switzerland) · 2022Review
- Cystine Knot Peptides with Tuneable Activity and Mechanism.Angewandte Chemie (International ed. in English) · 2022Article
- Yeast Surface Display: New Opportunities for a Time-Tested Protein Engineering System.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Engineered Cyclotides with Potent Broad in Vitro and in Vivo Antimicrobial Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Milking the Cow: Cattle-Derived Chimeric Ultralong CDR-H3 Antibodies and Their Engineered CDR-H3-Only Knobbody Counterparts Targeting Epidermal Growth Factor Receptor Elicit Potent NK Cell-Mediated Cytotoxicity.Frontiers in immunology · 2021Article
- Molecular evolution of peptides by yeast surface display technology.MedChemComm · 2019Review
- Potent, Selective, and Cell-Penetrating Inhibitors of Kallikrein-Related Peptidase 4 Based on the Cyclic Peptide MCoTI-II.ACS medicinal chemistry letters · 2018Article
- Selection of Antibodies with Tailored Properties by Application of High-Throughput Multiparameter Fluorescence-Activated Cell Sorting of Yeast-Displayed Immune Libraries.Molecular biotechnology · 2018Article
- Combinatorial engineering of N-TIMP2 variants that selectively inhibit MMP9 and MMP14 function in the cell.Oncotarget · 2018Article
- Designing macrocyclic disulfide-rich peptides for biotechnological applications.Nature chemical biology · 2018Article
- Engineering a potent inhibitor of matriptase from the natural hepatocyte growth factor activator inhibitor type-1 (HAI-1) protein.The Journal of biological chemistry · 2018Article
- Beyond antibody engineering: directed evolution of alternative binding scaffolds and enzymes using yeast surface display.Microbial cell factories · 2018Review
- Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.ACS chemical biology · 2018Article
- A novel one-step approach for the construction of yeast surface display Fab antibody libraries.Microbial cell factories · 2018Article
- Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystine-knot miniproteins define a class of bioactive molecules with several thousand natural members. Their eponymous motif comprises a rigid structured core formed by six disulfide-connected cysteine residues, which accounts for its exceptional stability towards thermic or proteolytic degradation. Since they display a remarkable sequence tolerance within their disulfide-connected loops, these molecules are considered promising frameworks for peptide-based pharmaceuticals. Natural open-chain cystine-knot trypsin inhibitors of the MCoTI (Momordica cochinchinensis trypsin inhibitor) and SOTI (Spinacia oleracea trypsin inhibitor) families served as starting points for the generation of inhibitors of matriptase-1, a type II transmembrane serine protease with possible clinical relevance in cancer and arthritic therapy. Yeast surface-displayed libraries of miniproteins were used to select unique and potent matriptase-1 inhibitors. To this end, a knowledge-based library design was applied that makes use of detailed information on binding and folding behavior of cystine-knot peptides. Five inhibitor variants, four of the MCoTI family and one of the SOTI family, were identified, chemically synthesized and oxidatively folded towards the bioactive conformation. Enzyme assays revealed inhibition constants in the low nanomolar range for all candidates. One subnanomolar binder (Ki = 0.83 nM) with an inverted selectivity towards trypsin and matriptase-1 was identified.
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