Abstract
Recent structural and kinetic studies indicated that enzymes shift their peripheral structures of the catalytic sites dynamically to modify the substrate structures. Molecules which disturb such mechanism of specific enzymes may become potent candidates for therapeutic reagent. This article describes a versatile strategy to synthesize new class of mechanism-based inhibitors for glycosyltransferases and glycoside hydrolases. Combination of irreversible tagging and proteomic analysis of crucial amino acid residues using MALDI-TOF/TOF mass spectrometry allowed a promising method to probe such invisible transitional state in the enzymatic reactions. Feasibility of the fluorescence energy resonance transfer (FRET) is also documented as novel protocol for the real-time and continuous monitoring of glycosyltransferase catalyzed reactions. It was demonstrated that FRET method greatly facilitates discovery research of selective inhibitors in combination with click chemistry.
Current Topics in Medicinal Chemistry
Title: Mechanism-Based Probing, Characterization, and Inhibitor Design of Glycosidases and Glycosyltransferases
Volume: 9 Issue: 1
Author(s): Hiroshi Hinou and Shin-Ichiro Nishimura
Affiliation:
Abstract: Recent structural and kinetic studies indicated that enzymes shift their peripheral structures of the catalytic sites dynamically to modify the substrate structures. Molecules which disturb such mechanism of specific enzymes may become potent candidates for therapeutic reagent. This article describes a versatile strategy to synthesize new class of mechanism-based inhibitors for glycosyltransferases and glycoside hydrolases. Combination of irreversible tagging and proteomic analysis of crucial amino acid residues using MALDI-TOF/TOF mass spectrometry allowed a promising method to probe such invisible transitional state in the enzymatic reactions. Feasibility of the fluorescence energy resonance transfer (FRET) is also documented as novel protocol for the real-time and continuous monitoring of glycosyltransferase catalyzed reactions. It was demonstrated that FRET method greatly facilitates discovery research of selective inhibitors in combination with click chemistry.
Export Options
About this article
Cite this article as:
Hinou Hiroshi and Nishimura Shin-Ichiro, Mechanism-Based Probing, Characterization, and Inhibitor Design of Glycosidases and Glycosyltransferases, Current Topics in Medicinal Chemistry 2009; 9 (1) . https://dx.doi.org/10.2174/156802609787354298
DOI https://dx.doi.org/10.2174/156802609787354298 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Neurogenesis as a New Target for the Development of Antidepressant Drugs
Current Pharmaceutical Design Autonomic Nervous System Alterations in Rett Syndrome
Current Pediatric Reviews Stat3 Orchestrates Tumor Development and Progression: The Achilles Heel of Head and Neck Cancers?
Current Cancer Drug Targets Cognitive Impairment and Dementia in Patients with Parkinson Disease
Current Topics in Medicinal Chemistry General Aspects of Metal Toxicity
Current Medicinal Chemistry NMR Screening and Hit Validation in Fragment Based Drug Discovery
Current Topics in Medicinal Chemistry Atypical Neuroleptic Malignant Syndrome or Serotonin Toxicity Associated with Atypical Antipsychotics?
Current Drug Safety Chemotherapeutic Strategies Against Trypanosoma brucei: Drug Targets vs. Drug Targeting
Current Pharmaceutical Design Protein Conformational Pathology in Alzheimers and Other Neurodegenerative Diseases; New Targets for Therapy
Current Alzheimer Research G Protein - Mediated Signaling: Same Receptor, Multiple Effectors
Current Molecular Pharmacology Overlapping Molecular Signatures in Parkinson's Patient Leukocytes Before and After Treatment and in Mouse Model Brain Regions
CNS & Neurological Disorders - Drug Targets Prodrugs and Endogenous Transporters: Are They Suitable Tools for Drug Targeting into the Central Nervous System?
Current Pharmaceutical Design Conformation as the Therapeutic Target for Neurodegenerative Diseases
Current Alzheimer Research Can Unconventional Exercise be Helpful in the Treatment, Management and Prevention of Osteosarcopenic Obesity?
Current Aging Science Neurobiology of Sleep Disturbances in Neurodegenerative Disorders
Current Pharmaceutical Design Value of Carnitine Therapy in Kidney Dialysis Patients and Effects on Cardiac Function from Human and Animal Studies
Current Drug Targets Inhibitors of Post-Translational Modifications of G-Proteins as Probes to Study the Pancreatic β Cell Function: Potential Therapeutic Implications
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Advantages of Structure-Based Drug Design Approaches in Neurological Disorders
Current Neuropharmacology Progress in the Use of Autologous Regenerative Platelet-based Therapies in Implant Dentistry
Current Pharmaceutical Biotechnology Parkinson Disease Genetics: A "Continuum" from Mendelian to Multifactorial Inheritance
Current Molecular Medicine