INHIBITORY EFFECT OF SYNTHETIC AMINOPHOSPHONIC ACID-DERIVATIVES ON HUMAN CARBONIC-ANHYDRASE

A series of phosphonic analogs of amino acids, peptides and their deri vatives was synthesized in order to examine their ability to inhibit h uman carbonic anhydrase (HCA) isoenzymes (I and II). The aminophosphon ic acids with amino protection possess much stronger inhibitory capaci ty (K(i) = 10(-6)-10(-5) M) than the free aminophosphonic acids (K(i) = 10(-5)-10(-3) M). The aminophosphonic acids with both N- and P-prote ction do not have an inhibitory effect on the esterase activity of HCA . In a comparison of the enantiomeric pairs of Cbz-AlaP(OH)2, the D-co nformer has several-fold stronger inhibitory potency. All aminoalkylph osphonates investigated possess one order of magnitude stronger inhibi tory activity towards isoenzyme HCA-I than towards HCA-II. A computer- directed analysis was used to study the possible interactions in an am inoalkylphosphonate [CbZ-D-AlaP(OH)2]-(HCA-II) complex.