Inhibition of aminopeptidases by phosphonic acid and phosphinic acid analogues of aspartic and glutamic acids.

More than 30 phosphonic and phosphinic acid analogues of aspartic and glutamic acids were synthesized in order to probe how the structural differences of these molecules were reflected in their ability to inhibit cytosolic (LAP) and microsomal (APM) aminopeptidases. Although most of the compounds studied were found to exert only a modest inhibitory effect, the studies provide some information on the structural requirements of the binding subsites and catalytic centers of both enzymes.

[1]  P. Wieczorek,et al.  Herbicidal activity of phosphonic and phosphinic acid analogues of glutamic and aspartic acids , 1992 .

[2]  J. Zygmunt,et al.  Inhibition of aminopeptidases by aminophosphonates. , 1989, Biochemistry.

[3]  P. Bartlett,et al.  Phosphorus amino acid analogues as inhibitors of leucine aminopeptidase. , 1987, Journal of medicinal chemistry.

[4]  A B Shenvi,et al.  alpha-Aminoboronic acid derivatives: effective inhibitors of aminopeptidases. , 1986, Biochemistry.

[5]  D. Rich,et al.  Pepstatin-derived inhibitors of aspartic proteinases. A close look at an apparent transition-state analogue inhibitor. , 1985, Journal of medicinal chemistry.

[6]  P. Kafarski,et al.  Chromatographic assignment of the configuration of 1-aminoalkane-phosphonic acids , 1985 .

[7]  R. Wolfenden,et al.  alpha-aminoaldehydes: transition state analogue inhibitors of leucine aminopeptidase. , 1982, Biochemistry.

[8]  J. Oleksyszyn,et al.  New phosphonic analogs of aspartic and glutamic acid by aminoalkylation of trivalent phosphorus chlorides with ethyl acetyloacetate or ethyl levulinate and benzyl carbamate , 1982 .

[9]  P. Bartlett,et al.  A phosphonamidate dipeptide analog as an inhibitor of carboxypeptidase A , 1981 .

[10]  B. Matthews,et al.  A crystallographic study of the complex of phosphoramidon with thermolysin. A model for the presumed catalytic transition state and for the binding of extended substances. , 1977, Journal of molecular biology.

[11]  R. Wolfenden,et al.  Transition state analog inhibitors and enzyme catalysis. , 1976, Annual review of biophysics and bioengineering.

[12]  E. D. Wachsmuth,et al.  An aminopeptidase occurring in pig kidney. II. A study on the mechanism of the hydrolysis. , 1966, Biochemistry.