Abstract
A new platelet antagonist, tokaracetin, was isolated from the venom of Trimeresurus tokarensis by ion-exchange chromatography, heparin-Sepharose chromatography and hydrophobic HPLC. The purified protein showed an apparent molecular mass on SDS/PAGE of 28.9 kDa under non-reducing conditions. On reduction, 16.1 and 15.4 kDa subunits were observed, suggesting that the molecule is a heterodimer. Tokaracetin inhibited the binding of 125I-labelled bovine von Willebrand factor (vWF) and 125I-labelled human vWF in the presence of botrocetin to fixed human platelets. It did not block ADP-, collagen- or thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (PRP), or induce platelet agglutination in PRP. On reduction, tokaracetin lost its inhibitory activity on the agglutination of fixed human platelets by bovine vWF. 125I-Tokaracetin specifically bound to washed human platelets with high affinity (Kd 3.9 +/- 1.4 nM) at 47,440 +/- 2780 binding sites per platelet. Binding of tokaracetin to fixed human platelets was reversible, and was inhibited by monoclonal antibody GUR83-35, which is directed against the N-terminal vWF-binding domain of human glycoprotein Ib (GPIb). Tokaracetin completely inhibited ...Continue Reading
Citations
May 3, 1996·The Journal of Biological Chemistry·T KawasakiK Titani
Feb 13, 2001·Blood·D DörmannK J Clemetson
Feb 3, 2005·British Journal of Haematology·Yumiko MatsubaraYasuo Ikeda
Jan 1, 2010·Toxins·Taei MatsuiKoiti Titani
Dec 12, 2017·BioMed Research International·Bruna Barbosa de SousaFábio de Oliveira
Feb 22, 2001·British Journal of Pharmacology·C H YehT F Huang
Jul 14, 1998·FEBS Letters·H MatsunoK Kato
Apr 6, 2001·Blood·A NavdaevK J Clemetson
Feb 24, 2000·Biochemistry·K FukudaT Morita
Aug 10, 2000·Biochemistry·C MarcinkiewiczS Niewiarowski
Jun 9, 1999·Biochemistry·R WangM C Chung
Feb 6, 2002·General Pharmacology·S LiT B Ng
Feb 25, 2000·Thrombosis Research·Y TaniuchiY Fujimura
Mar 1, 2000·Toxicon : Official Journal of the International Society on Toxinology·R K Andrews, M C Berndt
Jan 1, 1997·Peptides·K MaruyamaT Takenaka
Sep 15, 1999·Toxicon : Official Journal of the International Society on Toxinology·Y KomoriH Sugihara
Dec 5, 1998·Toxicon : Official Journal of the International Society on Toxinology·F S Markland
Oct 16, 2001·Toxicon : Official Journal of the International Society on Toxinology·H G ZhaY Zhang
Sep 19, 1996·European Journal of Pharmacology·N HisamichiN Ohshima
Nov 1, 1996·Toxicon : Official Journal of the International Society on Toxinology·R M Kini
Dec 5, 1998·Toxicon : Official Journal of the International Society on Toxinology·H C CastroR B Zingali
Mar 22, 2005·Toxicon : Official Journal of the International Society on Toxinology·Gufeng XuLiwen Niu
May 7, 2005·Toxicon : Official Journal of the International Society on Toxinology·Qiumin LuKenneth J Clemetson
Sep 20, 2005·Toxicon : Official Journal of the International Society on Toxinology·Brent JenningsEnid Shephard
Mar 4, 2009·Toxicon : Official Journal of the International Society on Toxinology·Etsuko OyamaHidenobu Takahashi