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.
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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 |
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