Advertisement

The Protein Journal

, Volume 30, Issue 3, pp 220–227 | Cite as

Stereoselective Inhibition of Cholesterol Esterase by Enantiomers of exo- and endo-2-Norbornyl-Nn-butylcarbamates

  • Ming-Cheng Lin
  • Shyh-Jei Yeh
  • I-Ru Chen
  • Gialih Lin
Article

Abstract

Four stereoisomers of 2-norbornyl-Nn-butylcarbamates are characterized as the pseudo substrate inhibitors of cholesterol esterase. Cholesterol esterase shows enantioselective inhibition for enantiomers of exo- and endo-2-norbornyl-Nn-butylcarbamates. For the inhibitions by (R)-(+)- and (S)-(−)-exo-2-norbornyl-Nn-butylcarbamates, the R-enantiomer is 6.8 times more potent than the S-enantiomer. For the inhibitions by (R)-(+)- and (S)-(−)-endo-2-norbornyl-Nn-butyl-carbamates, the S-enantiomer is 4.6 times more potent than the R-enantiomer. The enzyme-inhibitor complex models have been proposed to explain these different enantioselectivities.

Keywords

Cholesterol esterase Inhibitors Carbamates Enantiomers 

Abbreviations

ACS

Acyl chain binding site

CEase

Cholesterol esterase

LDL

Low-density lipoprotein

PNPB

p-nitrophenyl butyrate

TX

Triton-X 100

Notes

Acknowledgments

We thank the National Science Council of Taiwan for financial support.

References

  1. 1.
    Auer J, Eber B (1999) J Clin Basic Cardiol 2:203–208Google Scholar
  2. 2.
    Berson JA, Walla JS, Remanick A, Suzuki S, Reynods-Warnhoff P, Willner D (1961) J Am Chem Soc 83:3986–3997CrossRefGoogle Scholar
  3. 3.
    Brodt-Eppley J, White P, Jenkins S, Hui D (1995) Biochim Biophys Acta 1272:69–72Google Scholar
  4. 4.
    Chen JC-H, Miercke LJW, Krucinski J, Starr JR, Saenz G, Wang X, Spilburg CA, Lange LG, Ellsworth JL, Stroud RM (1998) Biochemistry 37:5107–5117CrossRefGoogle Scholar
  5. 5.
    Chiou S-Y, Huang C-F, Yeh S-J, Chen I-R, Lin G (2010) J Enzym Inhib Med Chem 25:13–20CrossRefGoogle Scholar
  6. 6.
    Chiou S-Y, Huang C-F, Yeh S-J, Chen I-R, Lin G (2010) Chirality 22:267–274Google Scholar
  7. 7.
    Chiou S-Y, Lai G-W, Lin L-Y, Lin G (2006) Ind J Biochem Biophys 43:52–55Google Scholar
  8. 8.
    Dale JA, Mosher HS (1973) J Am Chem Soc 95:512–519CrossRefGoogle Scholar
  9. 9.
    Feaster SR, Quinn DM (1997) Meth Enzymol 286:231–252CrossRefGoogle Scholar
  10. 10.
    Feaster SR, Lee K, Baker N, Hui DY, Quinn DM (1996) Biochemistry 35:16723–16734CrossRefGoogle Scholar
  11. 11.
    Hosie L, Sutton LD, Quinn DM (1987) J Biol Chem 262:260–264Google Scholar
  12. 12.
    Hui DY (1996) Biochim Biophys Acta 1302:1–14Google Scholar
  13. 13.
    Irwin AJ, Jones JB (1976) J Am Chem Soc 98:8476–8482CrossRefGoogle Scholar
  14. 14.
    Lopez-Candales A, Bosner MS, Spilburg CA, Lange LG (1993) Biochemistry 32:12085–12089CrossRefGoogle Scholar
  15. 15.
    Maron DJ, Fazio S, Linton MF (2000) Circulation 101:207–213Google Scholar
  16. 16.
    Nakazaki M, Chikamatsu H, Naemura K, Asao M (1980) J Org Chem 45:4432–4440Google Scholar
  17. 17.
    Pietsch M, Gütschow M (2002) J Biol Chem 277:24006–24013CrossRefGoogle Scholar
  18. 18.
    Pietsch M, Gütschow M (2005) J Med Chem 48:8270–8288CrossRefGoogle Scholar
  19. 19.
    Pioruńska-Stolzmann M, Piroruńska-Mikołajczak A (2002) Pharm Res 43:359–362CrossRefGoogle Scholar
  20. 20.
    Takahashi T, Fukuishima A, Tanaka Y, Takeuchi Y, Kabuto K, Kabuto C (2000) Chem Commun 788–789Google Scholar
  21. 21.
    Takahashi T, Kameda H, Kamei T, Ishizaki M (2006) J Fluorine Chem 127:760–768CrossRefGoogle Scholar
  22. 22.
    Wang C-S, Hartsuck JA (1993) Biochim Biophys Acta 1166:1–19Google Scholar
  23. 23.
    Wang X, Wang C-S, Tang J, Dyda F, Zhang XC (1997) Structure 5:1209–1218CrossRefGoogle Scholar
  24. 24.
    Winstein S, Trifan D (1951) J Am Chem Soc 74:1154–1160CrossRefGoogle Scholar
  25. 25.
    Yoshizako F, Nishimura A, Chubachi M, Kirihata M (1996) J Ferm Bioeng 82:601–603CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ming-Cheng Lin
    • 1
  • Shyh-Jei Yeh
    • 2
  • I-Ru Chen
    • 2
  • Gialih Lin
    • 2
  1. 1.Department of Internal Medicine, Chung Shan Medical University Hospital, School of MedicineChung-Shan Medical UniversityTaichungTaiwan
  2. 2.Department of ChemistryNational Chung-Hsing UniversityTaichungTaiwan

Personalised recommendations