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Related Concept Videos

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Antimicrobial Proteins

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Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
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An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
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Dimeric peptoids as antibacterial agents.

Ghayah Bahatheg1, Rajesh Kuppusamy2, Muhammad Yasir3

  • 1School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia; Department of Chemistry, Faculty of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.

Bioorganic Chemistry
|April 7, 2024
PubMed
Summary
This summary is machine-generated.

New dimeric peptoids show broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. These compounds disrupt bacterial cell membranes and biofilms with low toxicity, offering potential for novel antibacterial drug development.

Keywords:
Anti-biofilmAntibacterialMembrane disruptionPeptide mimicsPeptoids

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Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
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Area of Science:

  • Medicinal Chemistry
  • Antimicrobial Research
  • Biomaterials Science

Background:

  • Previous peptoid antibacterials were effective only against Gram-positive bacteria.
  • There is a need for new antibacterial agents effective against a broader range of pathogens, including Gram-negative bacteria.
  • Understanding the structure-activity relationship of peptoids is crucial for developing potent antimicrobial compounds.

Purpose of the Study:

  • To synthesize and evaluate novel dimeric peptoid compounds for antibacterial activity against Gram-positive and Gram-negative pathogens.
  • To investigate the mechanism of action of these peptoids, focusing on bacterial cell membrane disruption.
  • To assess the potential of these compounds in disrupting bacterial biofilms and their toxicity to mammalian cells.

Main Methods:

  • Synthesis of 34 dimeric peptoid compounds with varying hydrophobic and cationic moieties.
  • Antimicrobial susceptibility testing using minimum inhibitory concentration (MIC) assays against standard bacterial strains.
  • Mechanism of action studies including tethered bilayer lipid membranes (tBLMs) and cytoplasmic membrane permeability assays.
  • Biofilm disruption assays and cytotoxicity assessment against red blood cells.

Main Results:

  • A bromophenyl dimeric guanidinium peptoid (10j) demonstrated potent activity against *S. aureus* and *E. coli* (MICs of 0.8 and 6.2 μg/mL, respectively).
  • Peptoids were found to disrupt bacterial cell membranes, indicating a primary mechanism of action.
  • Several compounds showed negligible toxicity to mammalian red blood cells.
  • Ethyl and octyl-naphthyl guanidinium peptoids (10c and 10k) effectively disrupted established *S. aureus* biofilms.

Conclusions:

  • Dimeric peptoids with optimized hydrophobicity and cationicity exhibit broad-spectrum antibacterial activity.
  • These compounds act by disrupting bacterial cell membranes and show promise in combating biofilms.
  • The developed peptoids represent a new class of potential antibacterial agents with low mammalian toxicity.