Specific and potent inhibition of spermidine synthase by the transition-state analog, S-adenosyl-3-thio-1,8-diaminooctane

Kuo Chang Tang, Anthony Pegg, James K. Coward

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The title compound (1c), was designed and synthesized based on mechanistic data concerning enzyme-catalyzed alkyl transfer reactions, applied in this case to aminopropyl transferases. The inhibition by 1c of one such enzyme, spermidine synthase, was both potent (I50 = 4 × 10−7M) and specific. A closely related aminopropyltransferase, spermine synthase was only minimally affected by high concentrations of 1c. Similar, although not as marked, specifity between the two aminopropyltransferases was observed with the corresponding methyl sulfonium salt, 2c. Studies with structurally related compounds support the hypothesis that the strong inhibition of spermidine synthase by 1c derives from the incorporation in this compound of important features of the transition-state structure of this enzyme-catalyzed reaction.

Original languageEnglish (US)
Pages (from-to)1371-1377
Number of pages7
JournalTopics in Catalysis
Volume96
Issue number3
DOIs
StatePublished - Jan 1 1980

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Spermidine Synthase
Enzymes
Enzyme inhibition
Spermine Synthase
Transferases
Salts
S-adenosyl-3-thio-1,8-diaminooctane

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Specific and potent inhibition of spermidine synthase by the transition-state analog, S-adenosyl-3-thio-1,8-diaminooctane",
abstract = "The title compound (1c), was designed and synthesized based on mechanistic data concerning enzyme-catalyzed alkyl transfer reactions, applied in this case to aminopropyl transferases. The inhibition by 1c of one such enzyme, spermidine synthase, was both potent (I50 = 4 × 10−7M) and specific. A closely related aminopropyltransferase, spermine synthase was only minimally affected by high concentrations of 1c. Similar, although not as marked, specifity between the two aminopropyltransferases was observed with the corresponding methyl sulfonium salt, 2c. Studies with structurally related compounds support the hypothesis that the strong inhibition of spermidine synthase by 1c derives from the incorporation in this compound of important features of the transition-state structure of this enzyme-catalyzed reaction.",
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Specific and potent inhibition of spermidine synthase by the transition-state analog, S-adenosyl-3-thio-1,8-diaminooctane. / Tang, Kuo Chang; Pegg, Anthony; Coward, James K.

In: Topics in Catalysis, Vol. 96, No. 3, 01.01.1980, p. 1371-1377.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Specific and potent inhibition of spermidine synthase by the transition-state analog, S-adenosyl-3-thio-1,8-diaminooctane

AU - Tang, Kuo Chang

AU - Pegg, Anthony

AU - Coward, James K.

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AB - The title compound (1c), was designed and synthesized based on mechanistic data concerning enzyme-catalyzed alkyl transfer reactions, applied in this case to aminopropyl transferases. The inhibition by 1c of one such enzyme, spermidine synthase, was both potent (I50 = 4 × 10−7M) and specific. A closely related aminopropyltransferase, spermine synthase was only minimally affected by high concentrations of 1c. Similar, although not as marked, specifity between the two aminopropyltransferases was observed with the corresponding methyl sulfonium salt, 2c. Studies with structurally related compounds support the hypothesis that the strong inhibition of spermidine synthase by 1c derives from the incorporation in this compound of important features of the transition-state structure of this enzyme-catalyzed reaction.

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