ArticleJournal of medicinal chemistry2011
Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 68 citations in OpenAlex.
- Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations.Beilstein journal of organic chemistry · 2026Article
- Synthesis of Arginase Inhibitors: An Overview.Pharmaceutics · 2025Review
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
- Arginase inhibitory activities of guaiane sesquiterpenoids from Curcuma comosa rhizomes.Journal of natural medicines · 2023Article
- Virtual Screening for FDA-Approved Drugs That Selectively Inhibit Arginase Type 1 and 2.Molecules (Basel, Switzerland) · 2022Article
- Catalytic mechanism of DcsB: Arginase framework used for hydrolyzing its inhibitor.Protein science : a publication of the Protein Society · 2022Article
- Comprehensive Strategies to Bicyclic Prolines: Applications in the Synthesis of Potent Arginase Inhibitors.ACS medicinal chemistry letters · 2021Article
- Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology.ACS medicinal chemistry letters · 2021Article
- Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.Communications biology · 2021Article
- The First Insight Into the Supramolecular System ofFrontiers in chemistry · 2021Article
- A Broad Substrate Scope of Aza-Friedel-Crafts Alkylation for the Synthesis of Quaternary α-Amino Esters.Organic letters · 2020Article
- Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective.International journal of molecular sciences · 2020Review
- Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy.ACS medicinal chemistry letters · 2020Article
- Discovery and Pharmacokinetics of Sulfamides and Guanidines as Potent Human Arginase 1 Inhibitors.ACS medicinal chemistry letters · 2020Article
- Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158.Journal of structural biology: X · 2020Article
- The Neighboring Subunit Is Engaged to Stabilize the Substrate in the Active Site of Plant Arginases.Frontiers in plant science · 2020Article
- Structure and Function of the Acetylpolyamine Amidohydrolase from the Deep Earth HalophileBiochemistry · 2019Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New Modulation Possibilities.Scientific reports · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
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Authors and funding
5 authors at 5 institutions in 1 country.
Funding
Abstract
Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of α,α-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional α-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.
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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.