A brief overview of antimicrobial peptides containing unnatural amino acids and Ligand-based approaches for peptide Ligands

Jayendra B. Bhonsle, Tiffany Clark, Libero Bartolotti, Rickey P. Hicks

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 myco-bacterium 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.

Original languageEnglish (US)
Pages (from-to)3205-3224
Number of pages20
JournalCurrent Topics in Medicinal Chemistry
Volume13
Issue number24
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Antibacterial
  • Antimicrobial peptides
  • Multiple drug resistant pathogenic microorganisms
  • Physicochemical properties
  • QSAR

ASJC Scopus subject areas

  • Drug Discovery

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