Abstract
This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant antiidiotypic antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by β glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFvsusceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (β 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant antiidiotypic antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the β glucan KTR component in the cell walls of pathogenic microorganisms.
Keywords: yeast killer toxin, synthetic peptides, killer mimotopes, antimicrobial therapy, antiidiotypic antibiotics, antiidiotypic therapy
Current Medicinal Chemistry
Title: Engineered Killer Mimotopes: New Synthetic Peptides for Antimicrobial Therapy
Volume: 11 Issue: 13
Author(s): W. Magliani, S. Conti, A. Salati, S. Arseni, L. Ravanetti, R. Frazzi and L. Polonelli
Affiliation:
Keywords: yeast killer toxin, synthetic peptides, killer mimotopes, antimicrobial therapy, antiidiotypic antibiotics, antiidiotypic therapy
Abstract: This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant antiidiotypic antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by β glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFvsusceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (β 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant antiidiotypic antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the β glucan KTR component in the cell walls of pathogenic microorganisms.
Export Options
About this article
Cite this article as:
Magliani W., Conti S., Salati A., Arseni S., Ravanetti L., Frazzi R. and Polonelli L., Engineered Killer Mimotopes: New Synthetic Peptides for Antimicrobial Therapy, Current Medicinal Chemistry 2004; 11 (13) . https://dx.doi.org/10.2174/0929867043364964
DOI https://dx.doi.org/10.2174/0929867043364964 |
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
-
Insights into the Structural Features, Conformational Stability and Functional Activity of the <i>Olneya tesota</i> PF2 Lectin
Protein & Peptide Letters Graphical Abstracts
Letters in Drug Design & Discovery Protein Interactions Between the C-Terminus of Aβ-Peptide and Phospholipase A<sub>2</sub> - A Structure Biology Based Approach to Identify Novel Alzheimer's Therapeutics
CNS & Neurological Disorders - Drug Targets Chemical Intolerance
Current Rheumatology Reviews A Cytokine-Inducing Hemagglutinin from Small Taros
Protein & Peptide Letters Natural Oils as Skin Permeation Enhancers for Transdermal Delivery of Olanzapine: In Vitro and In Vivo Evaluation
Current Drug Delivery Players in ADP-ribosylation: Readers and Erasers
Current Protein & Peptide Science Multicomponent Pharmaceutical Cocrystals: A Novel Approach for Combination Therapy
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Evaluation of Scutellaria Flavone Cyclaneaminol Mannich Base Derivatives as Novel CDK1 Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Anti-Phospholipase A2 Receptor Autoantibody: A New Biomarker for Primary Membranous Nephropathy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Cyclophilins in Atherosclerosis: A New Therapeutic Target?
Current Pharmaceutical Design Synthetic Approaches and Pharmacological Attributes of Benzosuberone Skeleton
Mini-Reviews in Medicinal Chemistry Progress in Understanding Basal Ganglia Dysfunction as a Common Target for Methamphetamine Abuse and HIV-1 Neurodegeneration
Current HIV Research Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds
Recent Patents on Food, Nutrition & Agriculture Antivenoms for Snakebite Envenomings
Inflammation & Allergy - Drug Targets (Discontinued) Role of Free Radicals in Sepsis: Antioxidant Therapy
Current Pharmaceutical Design Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin
Current Pharmaceutical Design Protease Inhibitors in the Clinic
Medicinal Chemistry Regulation of TGF-β Signaling by SMADs and its Roles in Tissue Fibrosis
Current Signal Transduction Therapy Preface (Hot Topic: Fluorescence-based Screening Methods Guest Editor: Kyle R. Gee ).
Combinatorial Chemistry & High Throughput Screening