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.
Weiss
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B
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, New York, NY 10035.
Hui
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KS
Hui
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Lajtha
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A
D000596:Amino Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
D000596:Amino Acids; D063065:Organophosphonates; D000626:Aminopeptidases