1860-7187/asset/2452_left.gif?v=1&s=4110e7425ac5e40773dfb0778cfefa62f1594507)
1860-7187/asset/2452_right.gif?v=1&s=8458ea1f15af84217b579501ed7d7733bef04a94)
ChemMedChem
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Editor-in-Chief: Natalia Ortúzar
Impact Factor: 3.306
ISI Journal Citation Reports © Ranking: 2010: 10/54 (Chemistry Medicinal); 67/249 (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
Recently Published Issues
Current Issue:February 6, 2012
Volume 7, Issue 2
Volume 7, Issue 1
Volume 6, Issue 12
Volume 6, Issue 11
Volume 6, Issue 10
Latest News
February 04, 2012
VIP: Fluorogenic Peptide-Based Substrates for Monitoring Thrombin Activity
Sander 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.
Recently Published Articles
- Truncated Reverse Isoxazolidinyl Nucleosides: A New Class of Allosteric HIV-1 Reverse Transcriptase Inhibitors
Prof. Roberto Romeo, Dr. Salvatore V. Giofrè, Dr. Beatrice Macchi, Dr. Emanuela Balestrieri, Prof. Antonio Mastino, Pedro Merino, Dr. Caterina Carnovale, Prof. Giovanni Romeo and Prof. Ugo Chiacchio
Article first published online: 9 FEB 2012 | DOI: 10.1002/cmdc.201200022
Affairs of the HAART! The synthesis of HEPT-derived, truncated reverse isoxazolidinyl nucleosides (shown) is reported. These compounds represent the first examples of isoxazolidines bearing a pyrimidine scaffold at the C-3 position using a glycoside-type linkage. Biological evaluation showed that some of the derivatives act as non-nucleoside inhibitors of HIV-1 reverse transcriptase, with an efficacy comparable to that of Nevirapine but with reduced toxicity.
- Modulating Self-Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms
Tingyu Liu and Dr. Gal Bitan
Article first published online: 9 FEB 2012 | DOI: 10.1002/cmdc.201100585
Three strategies—one goal. The major mechanisms of drug candidates is discussed within three broad strategies: 1) stabilizing the monomer, 2) accelerating the pathway, and 3) modulating the pathway towards nontoxic assemblies. The merit of each strategy is assessed, prominent examples are given, and key points to consider when analyzing the efficacy and promise of a drug are discussed.
- Investigation of D1 Receptor–Agonist Interactions and D1/D2 Agonist Selectivity Using a Combination of Pharmacophore and Receptor Homology Modeling
Marcus Malo, Dr. Lars Brive, Prof. Kristina Luthman and Dr. Peder Svensson
Article first published online: 7 FEB 2012 | DOI: 10.1002/cmdc.201100546
The delicate balance between dopamine D1 and D2 agonism was investigated by using our combined receptor and pharmacophore modeling approach described in the preceding paper. Not only can the developed receptor models be used to understand the factors that determine receptor isoform selectivity, but also to design new dopamine receptor-selective agonists for use as potential therapeutic agents.
A Journal of ChemPubSoc Europe
1860-7187/asset/chempubsoc-eu.gif?v=1&s=38b47ef82a10e62d8a5b70c3f425403f4601eae4)