Conjugation of CRAMP Peptide to Chitosan and Hydroxypropyl Chitosan Via Copper-Catalyzed Azide-Alkyne Cycloaddition and Investigation of Antibacterial Activity

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Sep 14

PMID 39273387

Authors

Sankar Rathinam

Kasper K Sorensen

Martha A Hjalmarsdottir

Mikkel B Thygesen

Mar Masson

Affiliations

Soon will be listed here.

Abstract

We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The chitosan-peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan-peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, () and (), and two species of Gram-negative bacteria () and (). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria.

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