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
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
-
An Antifungal Peptide with Antiproliferative Activity Toward Tumor Cells from Red Kidney Beans
Protein & Peptide Letters EDITORIAL [Hot Topic: Molecularly Targeted Treatments for Colorectal Cancer: Advances and Limitations (Guest Editor: Silvio Parodi)]
Current Cancer Drug Targets Patent Selections:
Recent Patents on Food, Nutrition & Agriculture Death Receptor Signaling in Cancer Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Green Propolis: Thirteen Constituents of Polar Extract and Total Flavonoids Evaluated During Six Years through RP-HPLC
Current Drug Discovery Technologies Dual Inhibitors of β-Amyloid Aggregation and Acetylcholinesterase as Multi-Target Anti-Alzheimer Drug Candidates
Current Topics in Medicinal Chemistry DNA Demethylation by TET Proteins: A Potential Therapeutic Target in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) BRCA Mutational Status is a Promising Predictive Biomarker for Platinum- based Chemotherapy in Triple-Negative Breast Cancer
Current Drug Targets Topoisomerases and Tubulin Inhibitors: A Promising Combination for Cancer Treatment
Current Medicinal Chemistry - Anti-Cancer Agents Circulating Levels of Angiogenic Cytokines in Waldenstrom’s Macroglobulinemia: Clinical Correlations
Current Angiogenesis (Discontinued) Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication
Anti-Cancer Agents in Medicinal Chemistry Bronchomediastinal Fistula with Spontaneous Resolution in a Patient with Lung Cancer
Current Respiratory Medicine Reviews Recent Studies of QSAR on Inhibitors of Estrogen Receptor and Human Eosinophil Phosphodiesterase
Current Computer-Aided Drug Design Development and Application of Computational Methods in Biology and Medicine
Current Medicinal Chemistry Biological Potential of Halfsandwich Ruthenium(II) and Iridium (III) Complexes
Anti-Cancer Agents in Medicinal Chemistry Preparation and Characterization of a Heterogeneous Catalyst from Water Hyacinth (Eichhornia crassipes): Catalytic Application in the Synthesis of bis(indolyl)methanes and bis(pyrrolyl) methanes Under Solvent Free Condition
Current Catalysis Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation
Current Pharmacogenomics and Personalized Medicine γ-H2AX as a Therapeutic Target for Improving the Efficacy of Radiation Therapy
Current Cancer Drug Targets Immunotherapy of Kidney Cancer
Current Clinical Pharmacology A Proteomic Analysis of Human Uterine Myoma
Current Protein & Peptide Science