Abstract
Metallocarboxypeptidases (MCPs) are zinc-dependent exoproteases that have been for long considered benchmark enzymes, perform a wide range of physiological roles and have been regarded as interesting drug targets. Several crystal structures of MCPs in complex with protein and small molecular weight inhibitors have recently been obtained providing a framework for understanding the binding properties of these ligands. Much of the latest research focused on carboxypeptidase U or thrombin-activable fibrinolysis inhibitor (CPU/TAFI) which has fueled new designs in the field of cardiovascular drugs. Further, new details on the catalytic mechanism of MCPs have emerged from recent crystal structures of covalently modified forms and the pace of investigations on inhibitors has been steadily fastening in the last years. This paper will focus on the latest research carried on metallocarboxypeptidase small molecular weight inhibitors as drug candidates and will give an update of protein inhibitors to emphasize the growing interest for products isolated from natural sources.
Keywords: Metallocarboxypeptidase, inhibitor, mechanism-based inactivators, plasma enzymes, organic ligand, rational design
Current Medicinal Chemistry
Title:Metallocarboxypeptidases and their Inhibitors: Recent Developments in Biomedically Relevant Protein and Organic Ligands
Volume: 20 Issue: 12
Author(s): D. Fernandez, I. Pallares, G. Covaleda, F. X. Aviles and J. Vendrell
Affiliation:
Keywords: Metallocarboxypeptidase, inhibitor, mechanism-based inactivators, plasma enzymes, organic ligand, rational design
Abstract: Metallocarboxypeptidases (MCPs) are zinc-dependent exoproteases that have been for long considered benchmark enzymes, perform a wide range of physiological roles and have been regarded as interesting drug targets. Several crystal structures of MCPs in complex with protein and small molecular weight inhibitors have recently been obtained providing a framework for understanding the binding properties of these ligands. Much of the latest research focused on carboxypeptidase U or thrombin-activable fibrinolysis inhibitor (CPU/TAFI) which has fueled new designs in the field of cardiovascular drugs. Further, new details on the catalytic mechanism of MCPs have emerged from recent crystal structures of covalently modified forms and the pace of investigations on inhibitors has been steadily fastening in the last years. This paper will focus on the latest research carried on metallocarboxypeptidase small molecular weight inhibitors as drug candidates and will give an update of protein inhibitors to emphasize the growing interest for products isolated from natural sources.
Export Options
About this article
Cite this article as:
Fernandez D., Pallares I., Covaleda G., X. Aviles F. and Vendrell J., Metallocarboxypeptidases and their Inhibitors: Recent Developments in Biomedically Relevant Protein and Organic Ligands, Current Medicinal Chemistry 2013; 20 (12) . https://dx.doi.org/10.2174/0929867311320120009
DOI https://dx.doi.org/10.2174/0929867311320120009 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Bipolar Affective Disorder, Epilepsy and Migraine – Does Possible Shared Pathogenesis Explain their Association?
Current Psychopharmacology Glutamate-regulated Behavior, Transmitter Release, Gene Expression and Addictive Plasticity in the Striatum: Roles of Metabotropic Glutamate Receptors
Current Neuropharmacology Experimental Models for the Discovery of Novel Anticonvulsant Drugs: Focus on Pentylenetetrazole-Induced Seizures and Associated Memory Deficits
Current Pharmaceutical Design Is VEGF a Key Target of Cotinine and Other Potential Therapies Against Alzheimer Disease?
Current Alzheimer Research An Emerging Strategy for Cancer Treatment Targeting Aberrant Glycogen Synthase Kinase 3β
Anti-Cancer Agents in Medicinal Chemistry Heart Rate Variability Based Prediction of Personalized Drug Therapeutic Response: The Present Status and the Perspectives
Current Topics in Medicinal Chemistry Parallel Computing for Brain Simulation
Current Topics in Medicinal Chemistry Interaction of Macrocyclic Lactones with the Multidrug Transporters: The Bases of the Pharmacokinetics of Lipid-Like Drugs
Current Drug Metabolism New Antiepileptic Drugs: Molecular Targets
Central Nervous System Agents in Medicinal Chemistry High Throughput Electrophysiology with Xenopus Oocytes
Combinatorial Chemistry & High Throughput Screening Formulation Strategies of Nano Lipid Carrier for Effective Brain Targeting of Anti-AD Drugs
Current Pharmaceutical Design Functional Roles of Synaptic and Extrasynaptic NMDA Receptors in Physiological and Pathological Neuronal Activities
Current Drug Targets Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders
Current Drug Targets Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin
Current Neurovascular Research Inhibitors of Multidrug Efflux Transporters: Their Membrane and Protein Interactions
Mini-Reviews in Medicinal Chemistry Small Interfering RNAs and Antisense Oligonucleotides for Treatment of Neurological Diseases
Current Drug Targets Translocator Protein Ligands as Promising Therapeutic Tools for Anxiety Disorders
Current Medicinal Chemistry Role of COL4A1 in Basement-Membrane Integrity and Cerebral Small-Vessel Disease. The COL4A1 Stroke Syndrome
Current Medicinal Chemistry New Anticonvulsant Agents
Current Topics in Medicinal Chemistry New Avenue of Research: Antiepileptic Drug and Estradiol Neuroprotection in Epilepsy
Recent Patents on CNS Drug Discovery (Discontinued)