title: Wiedendiol-A inhibits cholesteryl ester binding to its transfer protein.
abstract: OBJECTIVE
  To study the wiedendiol-A (W-A) inhibition mechanism of plasma cholesteryl ester (CE) transfer protein (CETP) on the transfer of CE.
  
  
  METHODS
  Using gel filtration method.
  
  
  RESULTS
  W-A at 30 mumol.L-1 inhibited association of CE with CETP by 76% and CETP transfer activity by 81%. In addition, W-A enhanced binding of TP2, a monoclonal antibody with a CETP C-terminal epitope which is involved in CE binding, to CETP, suggesting a W-A-induced conformational change at the epitope for increased TP2 binding. When CETP activity was measured by varying high-density lipoproteins (HDL) concentration, the apparent Vmax of CE transfer was inhibited by 74% and 83% in the presence of W-A at 14 and 25 mumol.L-1, respectively, while the apparent K(m) of HDL for CETP did not change.
  
  
  CONCLUSIONS
  W-A action is mediated through interaction between W-A and CETP, but not through those between W-A and lipoproteins.
authors.affiliation: Department of CNS/CV Biological Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. wang@spcorp.com
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Clemmons
authors.forename: S
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: S J
authors.initials: SJ
authors.lastname: Coval
authors.forename: E
authors.initials: E
authors.lastname: Sybertz
authors.forename: R
authors.initials: R
authors.lastname: Burrier
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006023:Glycoproteins; D008075:Lipoproteins, HDL / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL