The ultimate goal of the project is to obtain new information on the catalytic action of vitamin B6-dependent enzymes by following their reactions with substrate analogues in which a carboxyl group is replaced by phosphonate or phosphinate. Such analogues should in many cases act as inhibitors or as very poor substrates due to the different chemistry of phosphorus as well as due to differences in charge and volume of the analogues. It should be possible to stabilise analogues of catalytic intermediates or Michaelis complexes which cannot be stabilised for the substrates themselves.

P-(1-aminoalkyl) phosphinic and P-(1-aminoalkyl) phosphonic acids of general formulae will be prepared that are analogues of a-methylalanine, a-methyl a-amino butyric acid, cycloleucine, tyrosine, nor-tyrosine, Phe, Asp and Glu. An improved synthesis for P-(1-aminoalkyl) phosphonic acid will be developed. The compound HO-CH2-CO-P(O)(OH)2, a presumed reversible blocking agent for lysine e-amino groups, will be synthesised. The reactions of such substrate analogues with the respective enzymes aspartate aminotransferase (AspAT), dialkylglycine decarboxylase (DGD) and DOPA decarboxylase will be tested in solution and in small crystals. In favourable cases the crystal structure of AspAT or DGD with such a ligand bound will be determined.