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Journal Articles Chemistry - A European Journal Year : 2021

Click and release chemistry for activity‐based purification of β‐lactam targets

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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.

Dates and versions

hal-03689982 , version 1 (07-06-2022)

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Saidbakhrom Saidjalolov, Emmanuelle Braud, Zainab Edoo, Laura Iannazzo, Filippo Rusconi, et al.. Click and release chemistry for activity‐based purification of β‐lactam targets. Chemistry - A European Journal, 2021, 27 (28), pp.7687-7695. ⟨10.1002/chem.202100653⟩. ⟨hal-03689982⟩
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