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Issue 1, 1998
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Aminoalkylphosphinate inhibitors of D-Ala-D-Ala adding enzyme

Abstract

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 µ>M>. 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.

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Article type: Paper
DOI: 10.1039/A704097K
Citation: J. Chem. Soc., Perkin Trans. 1, 1998,0, 131-142
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    Aminoalkylphosphinate inhibitors of D-Ala-D-Ala adding enzyme

    D. J. Miller, S. M. Hammond, D. Anderluzzi and T. D. H. Bugg, J. Chem. Soc., Perkin Trans. 1, 1998, 0, 131
    DOI: 10.1039/A704097K

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