Effect of several amino acid phosphonates and related compounds on rat brain aminopeptidases

N-Terminal sodium phosphonate derivatives Na3O3PCH2CONHR (R-Leu, Phe, or Tyr) and Na3O3PCH2CONHR-R (R-R = Leu-Phe, Phe-Leu, Phe-Phe, and Phe-Tyr) were synthesized. All showed no activity toward a soluble rat brain aminopeptidase. We could not prepare the corresponding N-2-phosphono-2,2-diphenylacetyl compounds (Na3O3PC(C6H5)2CONHR) by the same Arbusov reaction. Little or no inhibition was obtained with the N-(2-hydroxy-2,2-diphenylacetyl derivatives HOC(C6H5)2CONHR (R = Leu, Phe, Trp, or Tyr). The best inhibitory responses were given by the N-(2-halogeno-2,2-diphenylacetyl mono- and dipeptides (Br/Cl)C(C6H5)2CONH Phe and (Br/Cl)C(C6H5)2CONHR-R (R-R = Leu,Leu, Leu-Phe, Phe-Gly, Phe-Leu, or Phe-Phe), respectively.