Design and evaluation of analogues of the bacterial cell-wall peptidoglycan motif l-Lys-d-Ala-d-Ala for use in a vancomycin biosensor

Four small molecular receptors of vancomycin have been designed to make part of a novel biosensor device based on the FTIR-ATR detection: N-Boc (2a) or N-Ac (2b)-6-aminocaproyl-d-Ala-d-Ala and N-Boc (3a) or N-Ac (3b)-6-aminocaproyl-d-Ala-d-Ser. Using an original microbiological approach to assess the competition of compounds with the natural target of vancomycin in bacteria, EC50 values of 6.3–8.0 × 10−5 M (2a–b) and 7.1–9.3 × 10−4 M (3a–b) were determined. Vancomycin:2b complex was characterized by MS.