Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Inhibition of a Neutral Form of Sphingomyelinase by Alkylthioureido-l,3-propandiols, KY353X Series

  • Jung, Sang-Mi (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Jeong, Eui-Man (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Jo, Dong-Hwawn (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Chin, Mi-Reyoung (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Jun, Hyung-Jin (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Kim, Yong-Hyun (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Jeon, Hyung-Jun (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Lee, Dong-Hun (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Park, Mi-Ja (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Oh, Mi-Jung (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Yim, Chul-Bu (Department of Medical Chemistry, college of Pharmacy, Chung-Ang University) ;
  • Kim, Dae-Kyong (Department of Environmental & Health Chemistry, college of Pharmacy, Chung-Ang University)
  • Published : 2003.09.01
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Abstract

Alkylthioureido-1,3-propandiols (KY353X series) were synthesized and evaluated as inhibitors for neutral sphingomyelinase (N-SMase). To examine whether KY353X series inhibit N-SMase, we purified the N-SMase from bovine brain. The N-SMase was partially purified by sequential chromatographies of DEAE-Cellulose anionic exchange and phenyl-5PW hydrophobic HPLC. These seqeuntial procedures for N-SMase resulted in a 67-fold purification and excluded other isoforms of SMase. Based on in vitro assay, KY353X series inhibited N-SMase activity in time, concentration-dependent manners and completely inactivated N-SMase at 50 $\mu$M. In particular, KY3535 and KY3536 inhibited more effectively than the others. To further determine the .inhibitory pattern, a Dixon plot was constructed, to showing that the inhibition by KY3535 and KY3536 were competitive. The inhibition constant (Ki) of KY3535 and KY3536 was 1.7 $\mu$M and 2.5$\mu$M in 100 mM Tris-HCl buffer, pH 7.0, respectively.

Keywords

References

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