In:
Chemistry – A European Journal, Wiley, Vol. 27, No. 28 ( 2021-05-17), p. 7687-7695
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 Ldt fm 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.
Type of Medium:
Online Resource
ISSN:
0947-6539
,
1521-3765
DOI:
10.1002/chem.202100653
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1478547-X
detail.hit.zdb_id:
1231884-X
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