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Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan...
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Updated: Jan 8, 2026

Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
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Higher-Level Structural Classification of Pseudomonas Cyclic Lipopeptides through Their Bioactive Conformation.

Benjámin Kovács1, Durga Prasad1, Vic De Roo1

  • 1NMR and Structure Analysis Unit, Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Ghent, 9000, Belgium.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 14, 2025
PubMed
Summary

Pseudomonas cyclic lipodepsipeptides (CLiPs) adopt distinct helical structures, forming two superfamilies. This classification framework aids understanding of their function and potential applications in biocontrol and medicine.

Keywords:
conformational analysisleft‐handed α‐helixnon‐ribosomal biosynthesispseudomonas lipopeptidesstapled peptides

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Microbiology

Background:

  • Cyclic lipodepsipeptides (CLiPs) are Pseudomonas-derived metabolites with antimicrobial properties.
  • Understanding CLiP structure-function relationships is crucial for applications in plant biocontrol and medicine.
  • Limited 3D structural data hinders comprehensive analysis of CLiP diversity.

Purpose of the Study:

  • To determine the solution conformations of eight distinct Pseudomonas CLiPs.
  • To establish a new structural classification for Pseudomonas CLiPs.
  • To provide a foundation for future molecular design and functional studies.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy.
  • Molecular dynamics simulations in dodecylphosphocholine micelles.
  • Synthesis and structural analysis of a modified orfamide A analogue.

Main Results:

  • All studied CLiPs adopt left-handed α-helical conformations.
  • Two distinct helical motifs, 'stapled' and 'catch-pole', were identified based on macrocycle size.
  • These motifs define two superfamilies encompassing most known Pseudomonas CLiPs.
  • Structural classification correlates with the organization of CLiP biosynthetic gene clusters.

Conclusions:

  • A novel, coherent structural classification framework for Pseudomonas CLiPs has been established.
  • The identified structural dichotomy provides insights into CLiP function and evolution.
  • Findings facilitate homology modeling and rational design of CLiPs for targeted applications.