Can Immobilized Artificial Membrane Chromatography Support the Characterization of Antimicrobial Peptide Origin Derivatives?

Krzesimir Ciura,Wiesław Sawicki,Natalia Ptaszyńska,Anna Łęgowska,Monika Pastewska,Hanna Kapica,Katarzyna E Greber,Krzysztof Rolka,Wojciech Kamysz

doi:10.3390/antibiotics10101237

Krzesimir Ciura, Wiesław Sawicki + Show 7 more

Open Access

https://doi.org/10.3390/antibiotics10101237

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Journal: Antibiotics	Publication Date: Oct 12, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: Gdańsk Medical University, University of Gdańsk

Abstract

The emergence and spread of multiple drug-resistant bacteria strains caused the development of new antibiotics to be one of the most important challenges of medicinal chemistry. Despite many efforts, the commercial availability of peptide-based antimicrobials is still limited. The presented study aims to explain that immobilized artificial membrane chromatography can support the characterization of antimicrobial peptides. Consequently, the chromatographic experiments of three groups of related peptide substances: (i) short cationic lipopeptides, (ii) citropin analogs, and (iii) conjugates of ciprofloxacin and levofloxacin, with a cell-penetrating peptide were discussed. In light of the discussion of the mechanisms of action of these compounds, the obtained results were interpreted.

Highlights

The development of new antimicrobial agents is one of the most critical challenges of medicinal chemistry
The antibacterial mechanism of action of peptides and lipopeptides is mainly connected with the interactions between peptides and bacterial membranes [4], but some studies showed different results [5]
We investigated the possibility of using IAM-HPLC for the characterization of three groups of related peptide substances: (i) short cationic lipopeptides, (ii) citropin analogs, and (iii) conjugates of ciprofloxacin (CIP) and levofloxacin (LVX)

Summary

Introduction

The development of new antimicrobial agents is one of the most critical challenges of medicinal chemistry. Several natural and synthetic compounds have been explored and investigated to find new, effective, and safe antimicrobial agents. The antimicrobial peptides, lipopeptides, and other peptide origin derivatives, such as peptidomimetics, are very promising structures among the tested substances. They showed severe therapeutic potential due to their broad spectrum of activity, rapid bacterial killing, and synergy with classical antibiotics [1,2,3]. The antibacterial mechanism of action of peptides and lipopeptides is mainly connected with the interactions between peptides and bacterial membranes [4], but some studies showed different results [5]. The most recognized mechanisms of action are the barrel-stave model, carpet model, and toroidal model for killing pathogenic bacteria organisms [6]

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