Development of carbapenem-based fluorogenic probes for the clinical screening of carbapenemase-producing bacteria
- Development of carbapenem-based fluorogenic probes for the clinical screening of carbapenemase-producing bacteria
- 추현아; 김주현; Yihoon KIm; Ahmed Z. Abdelazem; Hak Joong Kim; Jung Ok Kim; Yeon-Joon Park; Sun-Joon Min; Hoon Seok Kim
- Carbapenems; carbapenemase-producing bacteria; linker; fluorescence; probes
- Issue Date
- Bioorganic chemistry
- VOL 94-14
- This report describes the synthesis of a library of fluorogenic carbapenemase substrates consisting of carbapenem derivatives, fluorescence dyes, and active cleavable linkers and their evaluation for specifically detecting carbapenemase-producing organisms (CPOs). We synthesized a series of compounds having three different types of linkers such as benzyl ether, carbamate, and amine using hydroxymethyl carbapenem 7a and hydroxyallyl carbapenem 7b as key intermediates. Probe 1b exhibited high stability and a prompt turn-on fluorescence signal upon hydrolysis by carbapenemases. In particular, the screening of clinical samples indicated that the probe 1b exhibited excellent selectivity to the CPOs over other β-lactamases or non-carbapenemase producing bacteria, which may be of clinical use for the rapid and accurate detection of CPOs for timely diagnosis and treatment.
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