Design, Synthesis, and Characterization of Non-hemolytic Antimicrobial Peptides Related to Human Cathelicidin LL-37

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 May 25

PMID 37228679

Authors

Rajavenkatesh Krishnamoorthy

Priyanka Adhikari

Parthiban Anaikutti

Affiliations

Soon will be listed here.

Abstract

We designed and synthesised the N-terminally labeled cationic and hydrophobic peptides, , FFKKSKEKIGKEFKKIVQKI (P1) and FRRSRERIGREFRRIVQRI (P2) related to the human cathelicidin LL-37 peptide. The integrity and molecular weight of the peptides were confirmed by mass spectrometry. The purity and homogeneity of peptides P1 and P2 were determined by comparing LCMS or analytical HPLC chromatograms. The circular dichroism spectroscopy reveals the conformational transitions upon interaction with membranes. Predictably, peptides P1 and P2 showed a random coil structure in the buffer and formed α-helix secondary structure in TFE and SDS micelles. This assessment was further confirmed by 2D NMR spectroscopic methods. The analytical HPLC binding assay measurements revealed that peptides P1 and P2 display preferential interactions with the anionic lipid bilayer (POPC:POPG) moderately than zwitterionic (POPC). The efficacies of the peptides were tested against Gram-positive and Gram-negative bacteria. It is imperative to note here that the arginine-rich P2 exerted higher activity against all the test organisms as compared with that shown by the lysine-rich peptide P1. To test the toxicity of these peptides, a hemolytic assay was performed. P1 and P2 showed very little to no toxicity for a hemolytic assay, which is significant for P1 and P2 to be used as potential therapeutic agents in practical applications. Both peptides P1 and P2 were non-hemolytic and appeared to be more promising as they demonstrated wide-spectrum antimicrobial activity.

Citing Articles

TC-14, a cathelicidin-derived antimicrobial peptide with broad-spectrum antibacterial activity and high safety profile.

Li C, Cai Y, Luo L, Tian G, Wang X, Yan A iScience. 2024; 27(7):110404.

PMID: 39092176 PMC: 11292558. DOI: 10.1016/j.isci.2024.110404.

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