期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 93, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2023.129428
关键词
Sortase A; Antibacterial photodynamic therapy; Fluorogenic labelling; Covalent ligation; Photosensitizer
Signal-on labeling and photodynamic destruction of Staphylococcus aureus (S. aureus) were achieved using self-quenched optical probes and Sortase A-mediated cleavage of a substrate motif. This dual biomarked-enabled peptidoglycan labeling approach shows potential for targeted therapy and diagnosis of SrtA-positive bacteria associated with various diseases.
Imaging or killing of a specific pathogen is of significance for precise therapy. Staphylococcus aureus (S. aureus) is an infectious gram-positive bacteria relying on Sortase A (SrtA) to anchor cell surface protein on peptidoglycan. We herein report signal-on labeling of S. aureus with self-quenched optical probes featuring vancomycin-conjugated SrtA substrate that is flanked by a dabcyl moiety paired with either fluorescein or eosine photo-sensizer (PS). SrtA-mediated cleavage of the substrate motif releases the dabcyl quencher, leading to covalent labeling of peptidoglycan with fluorescein or PS of restored photophysical property. The dual biomarked-enabled peptidoglycan labeling enables signal-on imaging and effective photodynamic destruction of S. aureus, suggesting a protheranostic approch activatable to SrtA-positive bacteria engaged in myriad diseases.
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