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
-
Proteomics Analysis: A Powerful Tool to Identify Proteome Phenotype and Proteome Signature in Enterococcus faecalis
Current Proteomics Staphylococcus aureus: Current State of Prevalence, Impact, and Vaccine Development
Current Pharmaceutical Design <i>Corynebacterium Striatum</i>, an Emerging Nosocomial Pathogen: Case Reports
Infectious Disorders - Drug Targets Selection Criteria for Probiotics and Potential of Cereal Based Food Products as Novel Probiotic-Carriers
Current Nutrition & Food Science Editorial [Hot topic: Infective Endocarditis (Guest Editor: Ioannis Starakis)]
Cardiovascular & Hematological Disorders-Drug Targets Design and Synthesis of Novel Anti-inflammatory/Anti-ulcer Hybrid Molecules with Antioxidant Activity
Medicinal Chemistry Recreational Drug Misuse and Stroke
Current Drug Abuse Reviews Short Term Statin Treatment Improves Survival and Differentially Regulates Macrophage-Mediated Responses to Staphylococcus aureus
Current Pharmaceutical Biotechnology Dissecting the Therapeutic Potency of Antimicrobial Peptides Against Microbial Biofilms
Current Protein & Peptide Science Arterial Ischemic Stroke in Neonates and Children: Review and Current Issues
Current Pediatric Reviews Susceptibility of Intracellular Coxiella burnetii to Antimicrobial Peptides in Mouse Fibroblast Cells
Protein & Peptide Letters Staphylococcus aureus: The Toxic Presence of a Pathogen Extraordinaire
Current Medicinal Chemistry Chest Pain in Children
Current Pediatric Reviews The Role of Universal Stress Proteins in Bacterial Infections
Current Medicinal Chemistry Perioperative Management of Patients with Down Syndrome
Current Pediatric Reviews Nutrition in Infancy
Current Pediatric Reviews Catastrophic Antiphospholipid Syndrome: Lessons from the “CAPS Registry”
Current Rheumatology Reviews Antibiotic Prophylaxis in Urologic Prosthetic Surgery
Current Pharmaceutical Design Long-term Outcomes of Mitral Valve Repair Versus Replacement for Degenerative Disease: A Systematic Review
Current Cardiology Reviews Immunoinformatic Approach for the Identification of Potential Epitopes Against <i>Stenotrophomonas maltophilia</i>: A Global Opportunistic Pathogen
Letters in Drug Design & Discovery