Patent ID: 6207399
Filing Date: 2001-03-27
Classification: A61K,C07K,C12Q,G01N,Y02P

Abstract:
A method for determining the ETP (endogenous thrombin potential) of a sample, said sample comprising at least 0.07 U ISH/ml due to at least one member selected from the group consisting of heparin and one or more other anticoagulants, resulting in a total anticoagulant activity or equivalent to at least 0.07 U ISH/ml, comprising using a thrombin substrate or a salt thereof that is soluble in the sample in the determination of the ETP of said sample, wherein said thrombin substrate is selected from the group consisting of:1) a dipeptide thrombin substrate comprising the formula P-Val-Xaa-S, wherein P is an amino protective group,said amino protective group is non-aromatic, polar, and fits in the aryl binding pocket of thrombin,Val is a valine residue attached via a peptide bond to Xaa,Xaa is an amino acid residue comprising a terminal guanidino group or ureido group separated by at least 2 carbon atoms from the peptide backbone, said amino acid residue being attached to S,S is a signal group that can be enzymatically hydrolyzed with the proviso that the substrate is not CH.sub.3 O--CO--CH.sub.2 --CO-L-Val-Arg-pNa or H-Val-Arg-p-nitroanilide (pNa),2) a thrombin substrate comprising the structure Zaa-Pipecolyl-Yaa-S or Zaa-Pro-Yaa-S, whereinZaa represents D-Phenylalanine, D-Tryptophan or D-Tyrosine,Pro represents proline,Yaa is an amino acid residue other than arginine andS is a signal marker,3) a thrombin substrate of the formula Boc-Gly-Val-Arg-p-nitroanilide or a salt thereof,4) a thrombin substrate of the formula H-Glu-Gly-Gly-Val-Arg-p-nitroanilide (SEQ ID NO:3) or a salt thereof and5) H-Val-Arg-pNa.