Specificity in enzyme inhibition. 2. .alpha.-Aminohydroxamic acids as inhibitors of histidine decarboxylase and 3,4-dihydroxyphenylalanine decarboxylase

Smissman, Edward E.; Warner, Victor D.

doi:10.1021/jm00276a031

Cited by 23 publications

(11 citation statements)

References 3 publications

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“…such as ␣-methyldopa either (Fig. 5C), which is a potent inhibitor for DDC but not for rHDC (39). The relatively large free binding region around the carboxylate group in hHDC (Fig.…”

Section: Discussionmentioning

confidence: 98%

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

Wu¹,

Gehring³

2007

FASEB j.

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Histamine, a biogenic amine with important biological functions, is produced from histidine by histidine decarboxylase (HDC), a pyridoxal 5'-phosphate-dependent enzyme. HDC is thus a potential target to attenuate histamine production in certain pathological states. Targeting mammalian HDC with novel inhibitors and elucidating the structural basis of their specificity for HDC are challenging tasks, because the three-dimensional structure of mammalian HDC is still unknown. In the present study, we designed, synthesized, and tested potentially membrane-permeable pyridoxyl-substrate conjugates as inhibitors for human (h) HDC and modeled an active site of hHDC, which is compatible with the experimental data. The most potent inhibitory compound among nine tested structural variants was the pyridoxyl-histidine methyl ester conjugate (PHME), indicating that the binding site of hHDC does not tolerate groups other than the imidazole side chain of histidine. PHME inhibited 60% of the fraction of 12-O-tetradecanoylphorbol-13-acetate-induced newly synthesized HDC in human HMC-1 cells at 200 microM and was also inhibitory in cell extracts. The proposed model of hHDC, containing phosphopyridoxyl-histidine in the active site, revealed the binding specificity of HDC toward its substrate and the structure-activity relationship of the designed and investigated compounds.

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“…such as ␣-methyldopa either (Fig. 5C), which is a potent inhibitor for DDC but not for rHDC (39). The relatively large free binding region around the carboxylate group in hHDC (Fig.…”

Section: Discussionmentioning

confidence: 98%

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

Wu¹,

Gehring³

2007

FASEB j.

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“…Commercially available reagents and solvents (Merck and Aldrich) were used without further purification. The sodium salt of glycine hydroxamic acid was synthesized as described previously . The starting {[LnCu 5 (GlyHA) 5 (SO 4 )(H 2 O) 6.5 ]} 2 (SO 4 )·6H 2 O (Ln = Pr, Nd, Sm, and Eu) were obtained according to previously reported procedures as dark blue polycrystalline powders, via the slow evaporation of aqueous solutions containing a 1:5:5 (equiv) ratio of Ln(NO 3 ) 3 · x H 2 O, CuSO 4 ·5H 2 O, and NaHGlyHA .…”

Section: Methodsmentioning

confidence: 99%

High Nuclearity Assemblies and One-Dimensional (1D) Coordination Polymers Based on Lanthanide–Copper 15-Metallacrown-5 Complexes (Ln^III = Pr, Nd, Sm, Eu)

et al. 2017

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Complexes {[LnCu(GlyHA)(m-bdc)(HO)][LnCu(GlyHA)(SO)(m-bdc)(HO)]}·(30 + 2x)HO (where GlyHA = glycinehydroxamate, m-bdc = m-phthalate; Ln = Pr and x = 0.21 for compound 1, or Ln = Sm and x = 0.24 for 3) and one-dimensional (1D) coordination polymers {[NdCu(GlyHA)(HO)(m-bdc)]n[NdCu(GlyHA)(HO)(μ-CO)(m-bdc)]}·13nHO (2) and {[EuCu(GlyHA)(HO)](m-bdc)[EuCu(GlyHA)(m-bdc)(HO)]}·17nHO (4) were obtained starting from the 15-metallacrown-5 complexes {[LnCu(GlyHA)(SO)(HO)]}(SO)·6HO (Ln = Pr, Nd, Sm, Eu) by the partial or complete metathesis of sulfate anions with m-phthalate. Compounds 1 and 3 contain unprecedented quadruple-decker neutral metallacrown assemblies, where the [LnCu(GlyHA)] cations are linked by m-phthalate dianions. In contrast, in complexes 2 and 4, these components assemble into 1D chains of coordination polymers, the adjacent {[NdCu(GlyHA)(HO)(m-bdc)]} 1D chains in 2 being separated by discrete [NdCu(GlyHA)(HO)(μ-CO)(m-bdc)]} complex anions. The crystal lattices of 2 and 4 contain voids filled by solvent molecules. Desolvated 4 is able to absorb up to 0.12 cm/g of methanol vapor or 0.04 cm/g of ethanol at 293 K. The isotherm for methanol absorption by compound 4 is consistent with a possible "gate opening" mechanism upon interaction with this substrate. The χT vs T data for complexes 1-4 and their simpler starting materials {[LnCu(GlyHA)(SO)(HO)]}(SO)·6HO (Ln(III) = Pr, Nd, Sm, Eu) were fitted using an additive model, which takes into account exchange interactions between lanthanide(III) and copper(II) ions in the metallamacrocycles via a molecular field model. The exchange interactions between adjacent Cu(II) ions in metallacrown fragments were found to fall in the range of -47 < J < -63 cm. These complexes are the first examples of a Ln(III)-Cu(II) 15-metallacrowns-5 (Ln(III) = Pr, Nd, Sm, Eu), for which values of exchange parameters have now been reported.

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“…The ligands glycine hydroxamic acid, l-leucine hydroxamic acid, l-valine hydroxamic acid, l-phenylalanine hydroxamic acid, and l-tyrosine hydroxamic acid were prepared via their respective methyl ester by following a literature method. [22] Characterization by 1 (1) were obtained by slow evaporation of an aqueous solution after synthesis. A single crystal was selected under the microscope and sealed in a thin-walled glass capillary.…”

Section: Methodsmentioning

confidence: 99%

Relaxometric Study of Copper [15]Metallacrown‐5 Gadolinium Complexes Derived from α‐Aminohydroxamic Acids

Parac‐Vogt

Pacco

Nockemann

et al. 2005

Chemistry A European J

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Proton nuclear magnetic relaxation dispersion (NMRD) profiles were recorded between 0.24 mT and 1.4 T for lanthanum(III)- and gadolinium(III)-containing [15]metallacrown-5 complexes derived from alpha-aminohydroxamic acids and with copper(II) as the ring metal. The influence of the different R-groups on the proton relaxivity was investigated, and a linear relationship between the relaxivity and the molecular mass of the metallacrown complex was found. The selectivity of the metallacrown complexes was tested by transmetalation experiments with zinc(II) ions. The crystal structure of the copper [15]metallacrown-5 gadolinium complex with glycine hydroximate ligands is reported.

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Specificity in enzyme inhibition. 2. .alpha.-Aminohydroxamic acids as inhibitors of histidine decarboxylase and 3,4-dihydroxyphenylalanine decarboxylase

Cited by 23 publications

References 3 publications

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

High Nuclearity Assemblies and One-Dimensional (1D) Coordination Polymers Based on Lanthanide–Copper 15-Metallacrown-5 Complexes (Ln^III = Pr, Nd, Sm, Eu)

Relaxometric Study of Copper [15]Metallacrown‐5 Gadolinium Complexes Derived from α‐Aminohydroxamic Acids

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Specificity in enzyme inhibition. 2. .alpha.-Aminohydroxamic acids as inhibitors of histidine decarboxylase and 3,4-dihydroxyphenylalanine decarboxylase

Cited by 23 publications

References 3 publications

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

Inhibitory and structural studies of novel coenzyme‐substrate analogs of human histidine decarboxylase

High Nuclearity Assemblies and One-Dimensional (1D) Coordination Polymers Based on Lanthanide–Copper 15-Metallacrown-5 Complexes (LnIII = Pr, Nd, Sm, Eu)

Relaxometric Study of Copper [15]Metallacrown‐5 Gadolinium Complexes Derived from α‐Aminohydroxamic Acids

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High Nuclearity Assemblies and One-Dimensional (1D) Coordination Polymers Based on Lanthanide–Copper 15-Metallacrown-5 Complexes (Ln^III = Pr, Nd, Sm, Eu)