Abstract
The shortcomings of native peptides as pharmaceuticals have been long known: short duration of action, lack of receptor selectivity, lack of oral bioavailability. However medicinal chemistry offers solutions to the first two limitations and oral bioavailability issues have been addressed with novel routes of administration (e.g. intranasal, inhalation) and injectable depot formulations. The principal issue for peptide drugs has been a short duration of action, widely assumed to be due to proteolysis. While proteolysis is a problem for native peptide structures, modification of the peptide structure by acylation, PEGylation, unnatural amino acids or restricted conformation can largely remove this issue. However rapid clearance from the blood into the urine remains an issue for even proteolytically stable molecules. Medicinal chemistry approaches here have been peptide modifications to slow release from the injection site (hydrophobic, hydrophilic, selfassociating depots), PEGylation, fatty acid acylation, and the like. Medicinal chemistry approaches used in successful peptide pharmaceuticals using unnatural amino acids to achieve depot formation are highlighted in this review.
Keywords: Peptide, peptide design, peptide pharmaceutical, drug design, medicinal chemistry, constrained peptide, pharmacodynamics, pharmacokinetics, drug depot
Current Medicinal Chemistry
Title: The Medicinal Chemistry of Peptides
Volume: 16 Issue: 33
Author(s): J. J. Nestor Jr.
Affiliation:
Keywords: Peptide, peptide design, peptide pharmaceutical, drug design, medicinal chemistry, constrained peptide, pharmacodynamics, pharmacokinetics, drug depot
Abstract: The shortcomings of native peptides as pharmaceuticals have been long known: short duration of action, lack of receptor selectivity, lack of oral bioavailability. However medicinal chemistry offers solutions to the first two limitations and oral bioavailability issues have been addressed with novel routes of administration (e.g. intranasal, inhalation) and injectable depot formulations. The principal issue for peptide drugs has been a short duration of action, widely assumed to be due to proteolysis. While proteolysis is a problem for native peptide structures, modification of the peptide structure by acylation, PEGylation, unnatural amino acids or restricted conformation can largely remove this issue. However rapid clearance from the blood into the urine remains an issue for even proteolytically stable molecules. Medicinal chemistry approaches here have been peptide modifications to slow release from the injection site (hydrophobic, hydrophilic, selfassociating depots), PEGylation, fatty acid acylation, and the like. Medicinal chemistry approaches used in successful peptide pharmaceuticals using unnatural amino acids to achieve depot formation are highlighted in this review.
Export Options
About this article
Cite this article as:
Nestor Jr. J. J., The Medicinal Chemistry of Peptides, Current Medicinal Chemistry 2009; 16 (33) . https://dx.doi.org/10.2174/092986709789712907
DOI https://dx.doi.org/10.2174/092986709789712907 |
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
-
Targeting Cardiac Mast Cells: Pharmacological Modulation of the Local Renin-Angiotensin System
Current Pharmaceutical Design Immune Checkpoint Inhibitors: Basics and Challenges
Current Medicinal Chemistry Epigenetic and miRNAs Dysregulation in Prostate Cancer: The role of Nutraceuticals
Anti-Cancer Agents in Medicinal Chemistry The Proline-Rich Domain and the Microtubule Binding Domain of Protein Tau Acting as RNA Binding Domains
Protein & Peptide Letters Effect of Cytostatic Drugs on the mRNA Expression Levels of Ribonuclease κ in Breast and Ovarian Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Novel Metals and Metal Complexes as Platforms for Cancer Therapy
Current Pharmaceutical Design Transcriptional Regulation of the p53 Tumor Suppressor Gene: A Potential Target for Cancer Therapeutics?
Recent Patents on DNA & Gene Sequences Killing the Messenger: Antisense DNA and siRNA
Current Drug Targets Protective Effect of Aspirin Against Oligomeric Aβ42 Induced Mitochondrial Alterations and Neurotoxicity in Differentiated EC P19 Neuronal Cells
Current Alzheimer Research Undesired Neural Side-Effects of a Drug, a Chemical and Genetic Interrelated Problem
Central Nervous System Agents in Medicinal Chemistry Roles of Glycogen Synthase Kinase 3 in Alzheimer’s Disease
Current Alzheimer Research Cannabinoids as Neuroprotective Agents in Traumatic Brain Injury
Current Pharmaceutical Design Malignant Mesothelioma: Cell Survival Pathways and Radiation Therapy
Current Respiratory Medicine Reviews An Integrated Drug Development Approach Applying Topological Descriptors
Current Computer-Aided Drug Design Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging
Current Drug Delivery Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling
Current Vascular Pharmacology Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors
Current Topics in Medicinal Chemistry TRAIL Agonists on Clinical Trials for Cancer Therapy: The Promises and the Challenges
Reviews on Recent Clinical Trials BCL-2 Family Proteins: The Mitochondrial Apoptotic Key Regulators
Current Cancer Therapy Reviews Neuroprotective Role of Agmatine in Neurological Diseases
Current Neuropharmacology