Abstract
The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development. In recent years, miniproteins and multicyclic peptides have become the preferred ligands expressed by these libraries. Due to their favorable pharmacokinetics and the ease of their synthesis, peptidic ligands overcome disadvantages of antibody derived therapeutics. Peptides that are structurally defined by a rigid scaffold are ideally suited for the use in display techniques. These molecules feature high stability and excellent affinities while offering the opportunity to randomize partial sequences to be used as binding sites. Structurization of the peptide scaffold can be achieved by different approaches, of which cyclization is one of the most commonly used. The favored cyclization strategies are based on amide or disulfide bridging and the use of synthetic braces or chemical linkers. The use of multicyclic peptides allows the simultaneous presentation of several different binding loops. Semisynthetic approaches enable the introduction of unnatural amino acids, increasing the diversity of the resulting peptide libraries. Given that, miniprotein scaffolds offer a wide range of potential applications and facilitate efficient screening of novel high-affinity ligands to be used in precise diagnosis and highly efficient cancer therapy.
Keywords: Drug development, miniprotein scaffolds, targeted therapy, peptide libraries, display techniques, highaffinity ligands.
Current Medicinal Chemistry
Title:Multicyclic Peptides as Scaffolds for the Development of Tumor Targeting Agents
Volume: 24 Issue: 20
Author(s): Anastasia Loktev, Uwe Haberkorn and Walter Mier*
Affiliation:
- Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120 Heidelberg,Germany
Keywords: Drug development, miniprotein scaffolds, targeted therapy, peptide libraries, display techniques, highaffinity ligands.
Abstract: The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development. In recent years, miniproteins and multicyclic peptides have become the preferred ligands expressed by these libraries. Due to their favorable pharmacokinetics and the ease of their synthesis, peptidic ligands overcome disadvantages of antibody derived therapeutics. Peptides that are structurally defined by a rigid scaffold are ideally suited for the use in display techniques. These molecules feature high stability and excellent affinities while offering the opportunity to randomize partial sequences to be used as binding sites. Structurization of the peptide scaffold can be achieved by different approaches, of which cyclization is one of the most commonly used. The favored cyclization strategies are based on amide or disulfide bridging and the use of synthetic braces or chemical linkers. The use of multicyclic peptides allows the simultaneous presentation of several different binding loops. Semisynthetic approaches enable the introduction of unnatural amino acids, increasing the diversity of the resulting peptide libraries. Given that, miniprotein scaffolds offer a wide range of potential applications and facilitate efficient screening of novel high-affinity ligands to be used in precise diagnosis and highly efficient cancer therapy.
Export Options
About this article
Cite this article as:
Loktev Anastasia, Haberkorn Uwe and Mier Walter *, Multicyclic Peptides as Scaffolds for the Development of Tumor Targeting Agents, Current Medicinal Chemistry 2017; 24 (20) . https://dx.doi.org/10.2174/0929867324666170316120304
DOI https://dx.doi.org/10.2174/0929867324666170316120304 |
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
-
Mitochondria as a Target for Exercise-Induced Cardioprotection
Current Drug Targets Glucosinolates – Secondary Plant Products as Important Complex Interaction in our Biosphere
Current Nutrition & Food Science Chemical Composition and Antioxidant Potential of Essential Oil and Organic Extracts of Euphorbia tithymaloides L. from Kushtia Region
Anti-Cancer Agents in Medicinal Chemistry Novel Insights Into c-Src
Current Pharmaceutical Design The Phosphoinositide 3-Kinase Pathway in Human Cancer: Genetic Alterations and Therapeutic Implications
Current Genomics Molecularly Targeted Therapy in Breast Cancer: The New Generation
Recent Patents on Anti-Cancer Drug Discovery Recent Advances In Developing Novel Anti-Cancer Drugs Targeting Tumor Hypoxic and Acidic Microenvironments
Recent Patents on Anti-Cancer Drug Discovery Application of Human Laboratory Models to Pharmacotherapy Development for Alcohol Dependence
Current Pharmaceutical Design Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery
Combinatorial Chemistry & High Throughput Screening PET Imaging of Multidrug Resistance in Tumors Using 18F-Fluoropaclitaxel
Current Topics in Medicinal Chemistry Non-Zinc-Binding Inhibitors of MMP-13: GRID-Based Approaches to Rationalize the Binding Process
Current Topics in Medicinal Chemistry Treatment of Nasopharyngeal Carcinoma: Therapeutic Management and Future View of Epstein-Barr Virus-Targeting Treatment
Current Cancer Therapy Reviews The Role of Redox Dysregulation in the Inflammatory Response to Acute Myocardial Ischaemia-reperfusion Injury - Adding Fuel to the Fire
Current Medicinal Chemistry Role of the Hypoxic Microenvironment in the Antitumor Activity of Tyrosine Kinase Inhibitors
Current Medicinal Chemistry Some Implications of Receptor Kinase Signaling Pathway for Development of Multitargeted Kinase Inhibitors
Current Radiopharmaceuticals Cellular and Physiological Effects of Ganoderma lucidum (Reishi)
Mini-Reviews in Medicinal Chemistry Epothilones: A Novel Class of Non-taxane Microtubule-stabilizing Agents
Current Pharmaceutical Design Hypoxia Helps Glioma to Fight Therapy
Current Cancer Drug Targets Current View on the Mechanism of Action of Perifosine in Cancer
Anti-Cancer Agents in Medicinal Chemistry Inflammatory Potential of Diet and the Risk of Prostate Cancer: A Casecontrol Study in the West of Iran
Current Nutrition & Food Science