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One‐Pot Synthesis of a Cyclic Antimicrobial Peptide‐Conjugated Phthalocyanine for Synergistic Chemo‐Photodynamic Killing of Multidrug‐Resistant Bacteria
Author(s) -
Chu Jacky C. H.,
Chin Miu Ling,
Wong Clarence T. T.,
Hui Mamie,
Lo PuiChi,
Ng Dennis K. P.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202000204
Subject(s) - peptide , photosensitizer , multiple drug resistance , conjugate , antimicrobial , photodynamic therapy , chemistry , phthalocyanine , conjugated system , combinatorial chemistry , bacteria , gram negative bacteria , cyclic peptide , microbiology and biotechnology , biochemistry , antibiotics , photochemistry , biology , organic chemistry , escherichia coli , gene , mathematical analysis , polymer , mathematics , genetics
Multidrug‐resistant (MDR) bacteria pose a serious threat to public health globally. Among the various antimicrobial modalities that have recently emerged, photodynamic therapy has received considerable attention because of its various potential advantages, including the unlikelihood of inducing drug resistance. A facile synthetic approach is reported to prepare a phthalocyanine‐based photosensitizer conjugated with a cyclic bactenecin peptide. This one‐pot procedure that involves site‐selective alkylation of the two cysteine residues of a linear bactenecin peptide followed by Diels–Alder reaction leads to the formation of the conjugate labeled as cBac‐Pc in 27% isolated yield. As shown by confocal fluorescence microscopy, this conjugate shows selective affinity toward bacterial over mammalian cells. It can also induce synergistic cytotoxic effects due to the cyclic peptide and phthalocyanine against a spectrum of Gram‐positive and Gram‐negative bacterial strains, including two ATCC‐type strains and two clinical isolates of MDR bacterial strains. It is believed that the inhibition mechanism is based on the physical destruction of the cell membrane due to the cyclic peptide followed by photodynamic action induced by the phthalocyanine unit.