Cover image for Vol. 12 Issue 15

Editorial Board Chairs: Karl-Heinz Altmann, Antonello Mai, Rainer Metternich. Editor: David Peralta

Impact Factor: 3.225

ISI Journal Citation Reports © Ranking: 2016: 17/60 (Chemistry Medicinal); 73/256 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

February 04, 2012

VIP: Fluorogenic Peptide-Based Substrates for Monitoring Thrombin Activity

VIP: Fluorogenic Peptide-Based Substrates for Monitoring Thrombin ActivitySander S. van Berkel, Bas van der Lee, Floris L. van Delft, Rob Wagenvoord, H. Coenraad Hemker, Floris P. J. T. Rutjes*

Thrombin plays a pivotal role in various pathological disturbances of the haemostatic system. Overexpression of thrombin can result in thrombosis, whereas its underexpression can lead to haemophilia. Therefore, accurate monitoring of thrombin activity is key to determining the proper course of treatment for a given patient. An accurate assessment of thrombin concentration in a blood sample can be used to estimate the blood's coagulation ability. A tool for monitoring the generation and disappearance of thrombin, and thus its concentration over time, is the so-called thrombin generation test (TGT).

In a collaborative project headed by Prof. Floris Rutjes (Radboud Univeristy Nijmegen (NL)) and Prof. Hemker (Cardiovascular Research Institute Maastricht (NL)), novel thrombin-specific fluorogenic peptides were developed for accurate assessments of thrombin concentrations using the TGT. Adding a thrombin-specific fluorogenic substrate to a clotting plasma sample results in thrombin-mediated hydrolysis of the substrate, releasing the fluorophore from the substrate. The use of a spectrophotometrically measurable fluorophore increases the sensitivity and thus accuracy of the TGT. Monitoring the increase in the induced signal over time gives rise to a thrombin generation curve, providing various essential coagulation parameters. The use of fluorogenic peptides in combination with the TGT is expected to find broad application in the field of haemostasis and thrombosis.

Received November 25, 2011; published online January 31, 2012, DOI: 10.1002/cmdc.201100560.

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