Synthesis and biochemical evaluation of cephalosporin analogues equipped with chemical tethers.

ABSTRACT: Molecular probes typically require structural modifications to allow for the immobilisation or bioconjugation with a desired substrate but the effects of these changes are often not evaluated. Here, we set out to determine the effects of attaching functional handles to a first-generation cephalosporin. A series of cephalexin derivatives was prepared, equipped with chemical tethers suitable for the site-selective conjugation of antibiotics to functionalised surfaces. The tethers were positioned remotely from the β-lactam ring to ensure minimal effect to the antibiotic's pharmacophore. Herein, the activity of the modified antibiotics was evaluated for binding to the therapeutic target, the penicillin binding proteins, and shown to maintain binding interactions. In addition, the deactivation

SUBMITTER: Miller LM 

PROVIDER: S-EPMC9056950 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature