Abstract
Antimicrobial Peptides (AMPs) incorporating unnatural Amino Acids have several advantages over naturally occurring AMPs based on factors such as bioavailability, metabolic stability and overall toxicity. Here we discuss the broad spectrum and organism specific bioactivity of unnatural amino acids incorporating AMPs against gram positive organisms such as S. aureus, E. faecium etc, gram negative organisms such as S. typhimurium, K. pneumonia etc and mycobacterium organisms such as M. ranae. We present comparative bioactivities of these AMPs against ESKAPE organism and select agent organisms such as Y. pesti, B. anthracis etc. The denovo design philosophy involving the three spacers approach with Spacer-1 defining flexibility, Spacer-2 determining overall surface charge density and Spacer-3 defining the conformational flexibility is discussed. The novel approach of differential computation of logP, Solvent-Accessible- Surface-Area , and Molecular Volume employing tripeptides with Gly as reference vis-à-vis various natural and unnatural amino acids, gives access to the estimation of the three important properties in the designed AMPs. An overview of the interaction studies employing Circular Dichroism (CD), Isothermal Titration Calorimetry (ITC) and induced Calcein leakage studies with these AMPs and various cell membranes mimics is presented.
Keywords: Antimicrobial peptides, multiple drug resistant pathogenic microorganisms, physicochemical properties, QSAR, antibacterial.
Current Topics in Medicinal Chemistry
Title:A Brief Overview of Antimicrobial Peptides Containing Unnatural Amino Acids and Ligand-Based Approaches for Peptide Ligands
Volume: 13 Issue: 24
Author(s): Jayendra B. Bhonsle, Tiffany Clark, Libero Bartolotti and Rickey P. Hicks
Affiliation:
Keywords: Antimicrobial peptides, multiple drug resistant pathogenic microorganisms, physicochemical properties, QSAR, antibacterial.
Abstract: Antimicrobial Peptides (AMPs) incorporating unnatural Amino Acids have several advantages over naturally occurring AMPs based on factors such as bioavailability, metabolic stability and overall toxicity. Here we discuss the broad spectrum and organism specific bioactivity of unnatural amino acids incorporating AMPs against gram positive organisms such as S. aureus, E. faecium etc, gram negative organisms such as S. typhimurium, K. pneumonia etc and mycobacterium organisms such as M. ranae. We present comparative bioactivities of these AMPs against ESKAPE organism and select agent organisms such as Y. pesti, B. anthracis etc. The denovo design philosophy involving the three spacers approach with Spacer-1 defining flexibility, Spacer-2 determining overall surface charge density and Spacer-3 defining the conformational flexibility is discussed. The novel approach of differential computation of logP, Solvent-Accessible- Surface-Area , and Molecular Volume employing tripeptides with Gly as reference vis-à-vis various natural and unnatural amino acids, gives access to the estimation of the three important properties in the designed AMPs. An overview of the interaction studies employing Circular Dichroism (CD), Isothermal Titration Calorimetry (ITC) and induced Calcein leakage studies with these AMPs and various cell membranes mimics is presented.
Export Options
About this article
Cite this article as:
Bhonsle B. Jayendra, Clark Tiffany, Bartolotti Libero and Hicks P. Rickey, A Brief Overview of Antimicrobial Peptides Containing Unnatural Amino Acids and Ligand-Based Approaches for Peptide Ligands, Current Topics in Medicinal Chemistry 2013; 13 (24) . https://dx.doi.org/10.2174/15680266113136660226
DOI https://dx.doi.org/10.2174/15680266113136660226 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Short Term Statin Treatment Improves Survival and Differentially Regulates Macrophage-Mediated Responses to Staphylococcus aureus
Current Pharmaceutical Biotechnology The Cancer Related Thrombotic Tendency in Sepsis
Current Drug Targets Cardiovascular Complications of HIV Infection and Treatment
Cardiovascular & Hematological Agents in Medicinal Chemistry Recent Tools to Overcome Antibacterial Resistance
Current Topics in Medicinal Chemistry The Impetus of COVID -19 in Multiple Organ Affliction Apart from Respiratory Infection: Pathogenesis, Diagnostic Measures and Current Treatment Strategy
Infectious Disorders - Drug Targets Uveitis in Rheumatic Diseases
Current Rheumatology Reviews Imidazole Derivatives and their Antibacterial Activity - A Mini-Review
Mini-Reviews in Medicinal Chemistry Pharmacological Treatments for Obesity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) A Review of Macrolide Treatment of Atherosclerosis and Abdominal Aortic Aneurysms
Current Drug Targets - Infectious Disorders Role of Old Antibiotics in Multidrug Resistant Bacterial Infections
Current Drug Targets The Role of Universal Stress Proteins in Bacterial Infections
Current Medicinal Chemistry Odontogenic Infections in the Etiology of Infective Endocarditis
Cardiovascular & Hematological Disorders-Drug Targets Current Concepts of Immunopathogenesis, Diagnosis and Therapy in Whipples Disease
Current Medicinal Chemistry Multiple Roles of Biosurfactants in Biofilms
Current Pharmaceutical Design Lantibiotic Production by Pathogenic Microorganisms
Current Protein & Peptide Science Clinical Presentations and Diagnosis of Brucellosis
Recent Patents on Anti-Infective Drug Discovery Prevention of Cardiovascular Complications in the Marfan Syndrome
Vascular Disease Prevention (Discontinued) Antimicrobial Strategies Effective Against Infectious Bacterial Biofilms
Current Medicinal Chemistry Thrombotic Microangiopathy and Occult Neoplasia
Cardiovascular & Hematological Disorders-Drug Targets Is There an Association between Periodontitis and Hypertension?
Current Cardiology Reviews