203806-00-2Relevant academic research and scientific papers
Aminoalkylphosphinate inhibitors of D-Ala-D-Ala adding enzyme
Miller, David J.,Hammond, Stephen M.,Anderluzzi, Daniela,Bugg, Timothy D. H.
, p. 131 - 142 (2007/10/03)
Pseudo-tri- and -tetra-peptide aminoalkylphosphinic acids of general structure X-LyS-PO2H-Gly-Ala have been synthesised as transition state analogues for D-Ala-D-Ala adding enzyme. The key synthetic step used to assemble the C-terminal dipeptide unit is a modified Arbusov reaction, coupling bromopropionyl-D-alanine methyl ester to a silylated aminoalkylphosphonite. Kinetic assays with the purified E. coli enzyme reveal that the phosphinate analogues act as reversible competitive inhibitors, with Ki values in the range 200-700 μM. Extended analogues mimicking the peptide chain of the UDPMurNAc-L-Ala-γ-D-Glu-m-DAP substrate show increased binding affinity for the enzyme active site. These are the first reported inhibitors for D-Ala-D-Ala adding enzyme.
