Specific and potent inhibition of spermidine synthase by the transition-state analog,S-adenosyl-3-thio-1,8-diaminooctane |
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Authors: | Kuo-Chang Tang Anthony E Pegg James K Coward |
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Institution: | 1. Department of Chemistry, Rensselaer Polytechnic Institute, Troy, N.Y. 12181 USA;2. Department of Physiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pa. 17033 USA. |
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Abstract: | The title compound (), was designed and synthesized based on mechanistic data concerning enzyme-catalyzed alkyl transfer reactions, applied in this case to aminopropyl transferases. The inhibition by 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 . Similar, although not as marked, specifity between the two aminopropyltransferases was observed with the corresponding methyl sulfonium salt, . Studies with structurally related compounds support the hypothesis that the strong inhibition of spermidine synthase by derives from the incorporation in this compound of important features of the transition-state structure of this enzyme-catalyzed reaction. |
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