Abstract
Metallocarboxypeptidases (MCPs) are commonly regarded as exopeptidases that actively participate in the digestion of proteins and peptides. In the recent years, however, novel MCPs comprising a wide range of physiological roles have been found in different mammalian extra-pancreatic tissues and fluids. Among them, CPU, also known as thrombinactivatable fibrinolysis inhibitor (TAFI), has been shown to cleave C-terminal Lys residues from partially degraded fibrin, acting as inhibitor of clot fibrinolysis and therefore constituting an important drug target for thrombolytic therapies. Other MCPs such as CPE, CPN, CPM, and CPD function as pro-hormone and neuropeptide processors and display several structural differences with the pancreatic-like enzymes. In addition, important advances have been made in the discovery and characterization of new endogenous and exogenous proteinaceous inhibitors; the structural determination of their complexes with several MCPs has revealed novel binding modes. Finally, the use of MCPs in antibody-directed enzyme pro-drug therapy (ADEPT) has proved to be an efficient approach for the delivery of lethal levels of chemotherapeutic drugs specifically at tumor tissues. Taken together, these recent developments may help to understand potential biomedical implications of MCPs. Future perspectives for the regulation of these enzymes through the use of more selective and potent inhibitors are also discussed in this review and combined with earlier observations in the field.
Keywords: Metallocarboxypeptidase, metallocarboxypeptidase inhibitor, inhibitor-enzyme complex, TAFI, pro-fibrinolytic drug, ADEPT and GDEPT, neuropeptide processing
Current Pharmaceutical Design
Title: Metallocarboxypeptidases: Emerging Drug Targets in Biomedicine
Volume: 13 Issue: 4
Author(s): Joan L. Arolas, Josep Vendrell, Francesc X. Aviles and Lloyd D. Fricker
Affiliation:
Keywords: Metallocarboxypeptidase, metallocarboxypeptidase inhibitor, inhibitor-enzyme complex, TAFI, pro-fibrinolytic drug, ADEPT and GDEPT, neuropeptide processing
Abstract: Metallocarboxypeptidases (MCPs) are commonly regarded as exopeptidases that actively participate in the digestion of proteins and peptides. In the recent years, however, novel MCPs comprising a wide range of physiological roles have been found in different mammalian extra-pancreatic tissues and fluids. Among them, CPU, also known as thrombinactivatable fibrinolysis inhibitor (TAFI), has been shown to cleave C-terminal Lys residues from partially degraded fibrin, acting as inhibitor of clot fibrinolysis and therefore constituting an important drug target for thrombolytic therapies. Other MCPs such as CPE, CPN, CPM, and CPD function as pro-hormone and neuropeptide processors and display several structural differences with the pancreatic-like enzymes. In addition, important advances have been made in the discovery and characterization of new endogenous and exogenous proteinaceous inhibitors; the structural determination of their complexes with several MCPs has revealed novel binding modes. Finally, the use of MCPs in antibody-directed enzyme pro-drug therapy (ADEPT) has proved to be an efficient approach for the delivery of lethal levels of chemotherapeutic drugs specifically at tumor tissues. Taken together, these recent developments may help to understand potential biomedical implications of MCPs. Future perspectives for the regulation of these enzymes through the use of more selective and potent inhibitors are also discussed in this review and combined with earlier observations in the field.
Export Options
About this article
Cite this article as:
Arolas L. Joan, Vendrell Josep, Aviles X. Francesc and Fricker D. Lloyd, Metallocarboxypeptidases: Emerging Drug Targets in Biomedicine, Current Pharmaceutical Design 2007; 13 (4) . https://dx.doi.org/10.2174/138161207780162980
DOI https://dx.doi.org/10.2174/138161207780162980 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Gum-Chewing and Headache: An Underestimated Trigger of Headache Pain in Migraineurs?
CNS & Neurological Disorders - Drug Targets Heart Disease Induced by AAS Abuse, Using Experimental Mice/Rats Models and the Role of Exercise-Induced Cardiotoxicity
Mini-Reviews in Medicinal Chemistry Recent Developments in the Treatment of Alcoholic Chronic Pancreatitis
Current Drug Abuse Reviews Modulators of Vascular Sex Hormone Receptors and their Effects in Estrogen-Deficiency States Associated with Menopause
Recent Patents on Cardiovascular Drug Discovery The Potential of Statins for Individualized Colorectal Cancer Chemoprevention
Current Drug Targets Review: Evidence-based Clinical Research of Anti-obesity Supplements in Japan
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cancer Chemoprevention by Targeting the Epigenome
Current Drug Targets Electronic Noses in Medical Diagnostics
Current Medicinal Chemistry Cardiovascular Drugs Inducing QT Prolongation: Facts and Evidence
Current Drug Safety Therapeutic Potential of Coagonists of Glucagon and GLP-1
Cardiovascular & Hematological Agents in Medicinal Chemistry Oral IIa and Xa Inhibitors for Prevention of Stroke in Atrial Fibrillation: Clinical Studies and Regulatory Considerations
Current Clinical Pharmacology Gender Bias in Acute Coronary Syndromes
Current Vascular Pharmacology The Role of Direct Oral Anticoagulant in Patients with Acute Coronary Syndrome on Single or Dual Antiplatelet Regime: Review of Opportunities and Challenges
Current Reviews in Clinical and Experimental Pharmacology Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation
Current Stem Cell Research & Therapy An Evolving Role of Piperazine Moieties in Drug Design and Discovery
Mini-Reviews in Medicinal Chemistry Xanthine Oxidase Inhibitors the Unappreciated Treatment for Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets May Oxygen-Ozone Therapy Improves Cardiovascular Disorders?
Cardiovascular & Hematological Disorders-Drug Targets Resveratrol Targets in Inflammation
Endocrine, Metabolic & Immune Disorders - Drug Targets HCN Channels Modulators: The Need for Selectivity
Current Topics in Medicinal Chemistry Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy
Current Pharmaceutical Design