摘要
几十年来,阿片受体一直是治疗疼痛有吸引力的治疗靶点。由于脑啡肽的发现,人们已经知道大约十几个内源性阿片肽可以产生阿片活性和镇痛作用,但他们的治疗方法受到限制,主要是由于低血脑屏障渗透和耐降解性差。一个通用的方法可以克服这些缺点,即针对环肽有限制的结构变化的线性肽环化。相比于它们线性的起源,环状类似物具有更好的代谢稳定性,较低的offtarget毒性,生物利用度的提高。针对有研究前景的化合物的广泛构效关系的研究已经发现用于治疗疼痛以及进一步阐明选择性阿片受体活性所需的结构元素。随之而来的好处是可以通过使用环多环衍生物的生成进一步增强其作用。阿片类药物一般都有短肽链,因此,目前还没有探讨多环肽的领域。在这篇综述中,对阿片受体配体的设计进行了简单的概括,包括经典的线性和环状配体,随着环肽配体的新方法和成功的受体的发展进入了深刻的讨论。阐述和总结了用来提高生物利用度的各种支架和方法,同时对于多环肽也进行了讨论。
关键词: 环肽,多环,阿片受体,镇痛,中枢神经系统,血脑屏障渗透,生物利用度。
Current Medicinal Chemistry
Title:Cyclic Opioid Peptides
Volume: 23 Issue: 13
Author(s): Michael Remesic, Yeon Sun Lee, Victor J. Hruby
Affiliation:
关键词: 环肽,多环,阿片受体,镇痛,中枢神经系统,血脑屏障渗透,生物利用度。
摘要: For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.
Export Options
About this article
Cite this article as:
Michael Remesic, Yeon Sun Lee, Victor J. Hruby , Cyclic Opioid Peptides, Current Medicinal Chemistry 2016; 23 (13) . https://dx.doi.org/10.2174/0929867323666160427123005
DOI https://dx.doi.org/10.2174/0929867323666160427123005 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Structural Activity Relationship and Importance of Benzothiazole Derivatives in Medicinal Chemistry: A Comprehensive Review
Mini-Reviews in Organic Chemistry Allopurinol Loaded Transferosomes for the Alleviation of Symptomatic After-effects of Gout: An Account of Pharmaceutical Implications
Current Drug Therapy MicroRNAs for Diagnosis and Treatment of Colorectal Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets A Glucuronidation Pathway of Capecitabine Occurs in Rats but Not in Mice and Humans
Drug Metabolism Letters Gene Microarray Analyses of Daboia russelli russelli Daboiatoxin Treatment of THP-1 Human Macrophages Infected with Burkholderia pseudomallei.
Current Molecular Medicine Multimodality Imaging of CXCR4 in Cancer: Current Status towards Clinical Translation
Current Molecular Medicine Synthesis and in vitro Anti-tumor Activity of Some New Sebacoyl Chloride Based Heterocycles
Current Organic Synthesis An Efficient One-Pot Organocatalyzed Synthesis of Spiro[Chroman-3,6'- Furo[2,3-d]Pyrimidine]-Tetraones
Combinatorial Chemistry & High Throughput Screening The Past, Current Studies and Future of Organometallic <sup>99m</sup>Tc(CO)3 Labeled Peptides and Proteins
Current Pharmaceutical Design Human Leukemia and Lymphoma Cell Lines as Models and Resources
Current Medicinal Chemistry Humic Acids as Therapeutic Compounds in Lead Intoxication
Current Clinical Pharmacology Chemical and Bioactive Diversities of the Genus Chaetomium Secondary Metabolites
Mini-Reviews in Medicinal Chemistry The ERp57/GRp58/1,25D3-MARRS Receptor: Multiple Functional Roles in Diverse Cell Systems
Current Medicinal Chemistry Bacterial Protein Microarrays for Diagnosis of Infectious Diseases
Current Immunology Reviews (Discontinued) Clinical Pharmacology of Serotonin Receptor Type 3 (5-HT3) Antagonists
Current Medicinal Chemistry - Central Nervous System Agents Familial Hypercholesterolemia: Update and Review
Endocrine, Metabolic & Immune Disorders - Drug Targets The Current Status of Antimalarial Drug Research with Special Reference to Application of QSAR Models
Combinatorial Chemistry & High Throughput Screening Database Construction and Peptide Identification Strategies for Proteogenomic Studies on Sequenced Genomes
Current Topics in Medicinal Chemistry A Five-gene Signature for Predicting the Prognosis of Colorectal Cancer
Current Gene Therapy A New and Effective Approach to the Synthesis of Sulforaphane
Letters in Organic Chemistry