ArticlePloS one2014
Potent and specific inhibition of glycosidases by small artificial binding proteins (affitins).
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- A protein-foldamer supramolecular synthon for self-assembled hybrid architectures.Nature chemistry · 2026Article
- Development of potent Affitin-based bispecific NK cell engagers for the therapy of MSLN-expressing cancers.Molecular therapy. Oncology · 2025Article
- Engineering and Structural Elucidation of a Sac7d-Derived IgG Fc-Specific Affitin and Its Application for the Light-Controlled Affinity Purification of Antibodies.Chembiochem : a European journal of chemical biology · 2025Article
- Complete preclinical evaluation of the novel antibody mimetic Nanofitin-IRDye800CW for diverse non-invasive diagnostic applications in the management of HER-2 positive tumors.Scientific reports · 2025Article
- Recent Applications of In Silico Approaches for Studying Receptor Mutations Associated with Human Pathologies.Molecules (Basel, Switzerland) · 2024Review
- Targeted Nanofitin-drug Conjugates Achieve Efficient Tumor Delivery and Therapeutic Effect in an EGFRpos Mouse Xenograft Model.Molecular cancer therapeutics · 2023Article
- Inhalable Nanofitin demonstrates high neutralization of SARS-CoV-2 virus via direct application in respiratory tract.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Nanofitins and their applications in human health and lung diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- CD98hc is a target for brain delivery of biotherapeutics.Nature communications · 2023Article
- Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins.Scientific reports · 2023Article
- Protein scaffolds: antibody alternatives for cancer diagnosis and therapy.RSC chemical biology · 2022Review
- Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager.Science translational medicine · 2022Article
- Evaluation of docking procedures reliability in affitins-partners interactions.Frontiers in chemistry · 2022Article
- New thermostable endoglucanase from Spirochaeta thermophila and its mutants with altered substrate preferences.Applied microbiology and biotechnology · 2021Article
- Characterization of Affitin proteolytic digestion in biorelevant media and improvement of their stabilities via protein engineering.Scientific reports · 2020Article
- Model Affitin and PEG modifications onto siRNA lipid nanocapsules: cell uptake andRSC advances · 2019Article
- Biophysical Characterization Platform Informs Protein Scaffold Evolvability.ACS combinatorial science · 2019Article
- A Cell-Surface GH9 Endo-Glucanase Coordinates with Surface Glycan-Binding Proteins to Mediate Xyloglucan Uptake in the Gut Symbiont Bacteroides ovatus.Journal of molecular biology · 2019Article
- Review
- Derivative of Extremophilic 50S Ribosomal Protein L35Ae as an Alternative Protein Scaffold.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1°C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general.
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Registered trials
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.