Journal
ADVANCED THERAPEUTICS
Volume 4, Issue 3, Pages -Publisher
WILEY
DOI: 10.1002/adtp.202000204
Keywords
antimicrobials; cyclization; peptides; photodynamic therapy; phthalocyanines
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Funding
- General Research Fund from the Research Grants Council of the Hong Kong Special Administrative Region, China [14304817]
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This study presents a facile synthetic approach to prepare a phthalocyanine-based photosensitizer conjugated with a cyclic bactenecin peptide, which shows selective affinity toward bacteria and synergistic cytotoxic effects against a spectrum of multidrug-resistant bacterial strains. The inhibition mechanism is believed to be based on the physical destruction of the cell membrane due to the cyclic peptide followed by photodynamic action induced by the phthalocyanine unit.
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.
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