Development of carbapenem-based fluorogenic probes for the clinical screening of carbapenemase-producing bacteria

Juhyeon Kim, Yihoon Kim, Ahmed Z. Abdelazem, Hak Joong Kim, Hyunah Choo, Hoon Seok Kim, Jung Ok Kim, Yeon Joon Park, Sun Joon Min

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number103405
JournalBioorganic Chemistry
Volume94
DOIs
Publication statusPublished - 2020 Jan

Keywords

  • Carbapenemase-producing bacteria
  • Carbapenems
  • Fluorescence
  • Linker
  • Probes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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