AI Article Synopsis
- - β-Lactams are crucial antibiotics that work by inhibiting enzymes known as transpeptidases or penicillin-binding proteins, which are essential for building bacterial cell walls.
- - Understanding how β-lactams work and how bacteria develop resistance requires effective methods to identify these enzymes as targets.
- - The study introduces a new method using "click and release" chemistry to purify β-lactam targets, employing specially designed alkyne-carbapenems that allow for efficient detection and analysis of these targets.
Article 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 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/chem.202100653 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!