2. Academic Validation
  3. Click and Release Chemistry for Activity-Based Purification of β-Lactam Targets

Click and Release Chemistry for Activity-Based Purification of β-Lactam Targets

  • Chemistry. 2021 May 17;27(28):7687-7695. doi: 10.1002/chem.202100653.
Saidbakhrom Saidjalolov 1,  Emmanuelle Braud 1,  Zainab Edoo 2,  Laura Iannazzo 1,  Filippo Rusconi 3,  Margaux Riomet 4,  Antoine Sallustrau 4,  Frédéric Taran 4,  Michel Arthur 2,  Matthieu Fonvielle 2,  Mélanie Etheve-Quelquejeu 1
Affiliations

Affiliations

  • 1 Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Université de Paris, 45, rue des saints-pères, Paris, 75006, France.
  • 2 INSERM UMRS 1138, Sorbonne Universités, UPMC Univ Paris 06, Sorbonne Paris Cité, Université de Paris, Centre de recherche des Cordeliers, Paris, 75006, France.
  • 3 PAPPSO, Université Paris-Saclay, INRAE, CNRS, AgroParisTech GQE - Le Moulon, Gif-sur-Yvette, 91190, France.
  • 4 Université Paris Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SCBM, Gif-sur-Yvette, 91191, France.
PMID: 33792096 DOI: 10.1002/chem.202100653
Abstract

β-Lactams, the cornerstone of antibiotherapy, inhibit multiple and partially redundant targets referred to as transpeptidases or penicillin-binding proteins. These Enzymes catalyze the essential cross-linking step of the polymerization of cell wall peptidoglycan. The understanding of the mechanisms of action of β-lactams and of resistance to these drugs requires the development of reliable methods to characterize their targets. Here, we describe an activity-based purification method of β-lactam targets based on click and release chemistry. We synthesized alkyne-carbapenems with suitable properties with respect to the kinetics of acylation of a model target, the Ldtfm L,D-transpeptidase, the stability of the resulting acylenzyme, and the reactivity of the alkyne for the cycloaddition of an azido probe containing a biotin moiety for affinity purification and a bioorthogonal Cleavable Linker. The probe provided access to the fluorescent target in a single click and release step.

Keywords

Activity-based probe; Antibiotic; Click and release; Iminosydnone; Peptidoglycan.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-207462
    L,D-transpeptidase抑制剂
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