Effect of several amino acid phosphonates and other compounds on rat brain and kidney peptidases.
A series of N-terminal phosphonate derivatives, H2O3PCHPhNHR (R = Leu, Phe, Trp, and/or Tyr), were synthesized with the aim of mimicking phosphoramidon, a potent inhibitor of enkephalinase, while avoiding the lability of the scissile P-N bond. All of the N-phosphonobenzyl derivatives of the amino acids, including the substituted succinylhydrazobenzophenone compounds, were inactive toward rat brain aminopeptidase and rat kidney carboxypeptidase. The N-monobenzylphosphonobenzyl derivatives, PhCH2OPO(OH)CHPhNHR, of individual amino acids and several of the N-phosphonobenzyl dipeptides showed inhibition in the micromolar range toward the soluble exopeptidase but were inactive with both the brain and kidney endopeptidase.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D010450:Endopeptidases; D007668:Kidney / Q000201:enzymology*; D015260:Neprilysin; D063065:Organophosphonates / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000700:Analgesics; D063065:Organophosphonates; D011480:Protease Inhibitors; D002268:Carboxypeptidases; D010450:Endopeptidases; D000626:Aminopeptidases; D015260:Neprilysin