Decarboxylase inhibition and structure-activity relationship studies with some newly synthetized benzyloxyamine and pyridylmethoxyamine derivatives

Huszti, Z.; Kasztreiner, E.; Szilágyi, G.; Kosary, J.; Borsy, J.

doi:10.1016/0006-2952(73)90007-5

Cited by 11 publications

(4 citation statements)

References 25 publications

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“…Anal. (CK,H19C12N302) C, , N. IV-Methyl DL-/3-(4-Imidazolyl)propionamide Dihydrochloride (11). A solution of 0.97 g (4.0 mmol) of DL-histidine methyl ester27 in 25 mL of MeOH was saturated with MeNH2 at 0 °C and then heated in a stainless steel bomb at 50 °C for 18 h. The solvent was evaporated; the residue was dissolved in about 50 mL of H20 and then stirred with excess ion-exchange resin [Rexyn 201(OH)] until a negative AgNOs test was obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Esterification of 14 and 2724 catalyzed by thionyl chloride25 in methanol proceeded smoothly to give 15 and 28. Esterification of histidine, however, with 1-propanol or 1-butanol in the presence of hydrogen chloride26 or thionyl chloride25 proceeded sluggishly with only low yield of analytically pure material. The amide 11 was available from DL-histidine methyl ester27 and methylamine.…”

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confidence: 99%

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Inhibition of histidine decarboxylase. Derivatives of histidine

Kelley¹,

Miller²,

White³

1977

J. Med. Chem.

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Twenty-eight derivatives of histidine were tested as inhibitors of histidine decarboxylase from rat stomach. Potent inhibition was observed with the methyl ester of L-histidine (1) which had a Ki = 1.8 X 10(-6) M. Substitution on 1 at various positions resulted in a decrease or complete loss of inhibition. Substituent requirements for inhibition of histidine decarboxylase are discussed. A simple disposable apparatus for the radiometric assay of histidine decarboxylase is described.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of histidine decarboxylase. Derivatives of histidine

Kelley¹,

Miller²,

White³

1977

J. Med. Chem.

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“…There is apparently some leeway in the catalytic site around the a-carbon, but only in the direction distal to histidine carbon-1 is there reasonable steric freedom as judged from the fact that alkylesters up to butyl are inhibitory [9]. The strong inhibition observed with benzyl and pyridyl substituted methoxyamines [22] suggests a hydrophobic area close to the catalytic center. Against this background it would seem likely that peptides with histidine at the amino terminus could act as inhibitors (d, Scheme 1).…”

Section: Introductionmentioning

confidence: 91%

“…However, some selectivity has been observed with different methoxyamines. HUSZTI et al [22] for instance, report that 3-nitrobenzyloxyamine and pyridyl-3-methoxyamine have about 20-fold higher affinity for histidine decarboxylase than for aromatic Lamino acid decarboxylase, while some other benzyloxyamines and pyridylmethoxyamines were about equally potent with the two enzymes. The cited reports on histidine analog inhibition suggest that the substrate binding site is a narrow pocket highly specific for hlstidine.…”

Section: Introductionmentioning

confidence: 96%

Peptide inhibition of mammalian histidine decarboxylase

Hammar

Ragnarsson

1979

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The hypothesis that N-terminal histidine peptides might act as inhibitors to histidine decarboxylase was investigated. A murine mastocytoma was utilized as enzyme source. The crude extract of this tissue exhibits high rates of decarboxylation of both histidine and DOPA and was used to establish the specificity in the effect of the compounds tested. For kinetic analyses a highly purified histidine decarboxylase fraction was used. The effect of some representative peptides on both enzyme activities were recorded. Histidine decarboxylase exclusively was inhibited by N-terminal histidine peptides. None of the other peptides investigated interfered negatively with this enzyme. This inhibition was consistent in the purified preparation and appeared to be more pronounced with increasing hydrophobicity in the second amino acid. Histidyl-phenylalanine was found to be about 100-fold as potent as the commonly used specific histidine decarboxylase inhibitor alpha-methyl histidine. It is concluded that small peptides with histidine as the N-terminal amino acid might act as specific inhibitors for mammalian histidine decarboxylase. An analog effect of small tyrosyl or phenylalanyl peptides was not seen for the DOPA decarboxylase.

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