Inhibition of bovine plasma amine oxidase by 1,4-diamino-2-butenes and -2-butynes

Jeon, Heung-Bae; Lee, Younghee; Qiao, Chunhua; Huang, He; Sayre, Lawrence M.

doi:10.1016/s0968-0896(03)00521-2

Cited by 29 publications

(27 citation statements)

References 26 publications

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“…Although it is unlikely that these drugs could be refined to preclude binding to all human CuAOs to help alleviate the side‐effects involved in their use as antidepressants acting on flavin‐containing amine oxidases, the exquisite substrate specificity of the CuAOs could allow these types of drugs to act as lead compounds in the rational design of drugs against HuPAO, whose action is linked to the vascular changes in late diabetic complications and congestive heart disease. As the human CuAOs are further studied, links to other diseases are likely to emerge, and the inherent differing specificities of these enzymes may allow a new palette of drugs to be designed from this original class of MAOI antidepressants to complement other mechanism‐based compounds [36,37] or peptides [38].…”

Section: Resultsmentioning

confidence: 99%

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

Wilmot¹,

Saysell²,

Blessington³

et al. 2004

FEBS Letters

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The X-ray crystal structure of the copper-containing quinoprotein amine oxidase from E. coli has been determined in complex with the antidepressant drug tranylcypromine to 2.4 A resolution. The drug is a racemic mix of two enantiomers, but only one is seen bound to the enzyme. The other enantiomer is not acting as a substrate for the enzyme as no catalytic activity was detected when the enzyme was initially exposed to the drug. The inhibition of human copper amine oxidases could be a source of side-effects in its use as an antidepressant to inhibit the flavin-containing monoamine oxidases in the brain.

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Section: Resultsmentioning

confidence: 99%

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

Wilmot¹,

Saysell²,

Blessington³

et al. 2004

FEBS Letters

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“…In these features, the reaction does not differ from those of typical plant CAO substrates like putrescine or cadaverine. GPAO and OVAO inactivation caused by the substrate DAPY fulfills the criteria of a mechanismbased inhibition: it is time dependent, irreversible and can be weakened in the presence of a normal substrate [5,7,11,22].…”

Section: Discussionmentioning

confidence: 99%

“…There are detailed reports on the mechanism-based inhibition of CAOs by DABY in the literature [7][8][9][10][11]. The authors have shown that DABY is oxidized to 4-amino-2-butynal, which induces inactivation by adducting to a nucleophile in the substrate channel.…”

Section: Discussionmentioning

confidence: 99%

“…Lysine residues in plant CAOs are possible targets for covalent binding of reactive electrophilic aminoaldehydes formed by the turnover of acetylenic diamine substrates [7][8][9][10][11]. The cDNA of GPAO subunit (without the signal peptide) has been cloned and sequenced (D. Kopecˇny´, N. Houba-He´rin, H. G. Faulhammer & M. Sˇebela, unpublished results; EMBL/GenBank accession number AJ786401).…”

Section: Other Analysesmentioning

confidence: 99%

“…Namely, the inactivating effect of DABY (as a putrescine analog) on plant CAOs has been studied in detail at the molecular level [8][9][10]. Various b-unsaturated compounds were tested in the reaction with bovine plasma CAO [10][11][12][13]. Propargylic and chloroallylic diamines were highly potent inhibitors of the enzyme, more so than simple allylic diamines [11][12][13].…”

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confidence: 99%

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1,5‐Diamino‐2‐pentyne is both a substrate and inactivator of plant copper amine oxidases

Lamplot¹,

Šebela²,

Maloň³

et al. 2004

European Journal of Biochemistry

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1,5-Diamino-2-pentyne (DAPY) was found to be a weak substrate of grass pea (Lathyrus sativus, GPAO) and sainfoin (Onobrychis viciifolia, OVAO) amine oxidases. Prolonged incubations, however, resulted in irreversible inhibition of both enzymes. For GPAO and OVAO, rates of inactivation of 0.1-0.3 min )1 were determined, the apparent K I values (half-maximal inactivation) were of the order of 10DAPY was found to be a mechanism-based inhibitor of the enzymes because the substrate cadaverine significantly prevented irreversible inhibition. The N 1 -methyl and N 5-methyl analogs of DAPY were tested with GPAO and were weaker inactivators (especially the N 5 -methyl) than DAPY. Prolonged incubations of GPAO or OVAO with DAPY resulted in the appearance of a yellow-brown chromophore (k max ¼ 310-325 nm depending on the working buffer). Excitation at 310 nm was associated with emitted fluorescence with a maximum at 445 nm, suggestive of extended conjugation. After dialysis, the color intensity was substantially decreased, indicating the formation of a low molecular mass secondary product of turnover. The compound provided positive reactions with ninhydrin, 2-aminobenzaldehyde and Kovacs' reagents, suggesting the presence of an amino group and a nitrogen-containing heterocyclic structure. The secondary product was separated chromatographically and was found not to irreversibly inhibit GPAO. MS indicated an exact molecular mass (177.14 Da) and molecular formula (C 10 H 15 N 3 ). Electrospray ionization-and MALDI-MS/MS analyses yielded fragment mass patterns consistent with the structure of a dihydropyridine derivative of DAPY. Finally, N-(2,3-dihydropyridinyl)-1,5-diamino-2-pentyne was identified by means of 1 H-and 13 C-NMR experiments. This structure suggests a lysine modification chemistry that could be responsible for the observed inactivation.

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Highly Selective Synergistic Copper(I/II)‐Catalyzed A³ Cross Coupling/Decarboxylative A³ Domino Reactions in Water

et al. 2016

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A microwave‐assisted copper‐catalyzed A3 cross‐coupling/decarboxylative A3 domino reaction of a propiolic acid, an aldehyde, a formaldehyde solution and an amine is described. This strategy represents the first one‐pot cross‐coupling reaction for the direct synthesis of trisubstituted unsymmetrical 2‐butynes with a broad functional group tolerance in good yields (up to 91 %) and excellent chemoselectivity. The simultaneous activation of both the C−COOH and C−H bond of propiolic acid is crucial in this approach, and only carbon dioxide and water are generated as byproducts.

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Inhibition of bovine plasma amine oxidase by 1,4-diamino-2-butenes and -2-butynes

Cited by 29 publications

References 26 publications

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

1,5‐Diamino‐2‐pentyne is both a substrate and inactivator of plant copper amine oxidases

Highly Selective Synergistic Copper(I/II)‐Catalyzed A³ Cross Coupling/Decarboxylative A³ Domino Reactions in Water

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Inhibition of bovine plasma amine oxidase by 1,4-diamino-2-butenes and -2-butynes

Cited by 29 publications

References 26 publications

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

Medical implications from the crystal structure of a copper‐containing amine oxidase complexed with the antidepressant drug tranylcypromine

1,5‐Diamino‐2‐pentyne is both a substrate and inactivator of plant copper amine oxidases

Highly Selective Synergistic Copper(I/II)‐Catalyzed A3 Cross Coupling/Decarboxylative A3 Domino Reactions in Water

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Product

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About

Highly Selective Synergistic Copper(I/II)‐Catalyzed A³ Cross Coupling/Decarboxylative A³ Domino Reactions in Water