Current Pharmaceutical Design - Volume 10, Issue 9, 2004

Heparin and other iduronic acid-containing glycosaminoglycans (GAG) such as dermatan sulfate exert their anticoagulant properties primarily by accelerating the rate of inhibition of the natural protease inhibitors antithrombin III (AT, which inhibits both factor Xa and thrombin) and heparin cofactor II (HCII, which selectively inhibits thrombin). Although AT and HCII are structural homologs, only heparin binds to AT, and HCII h Read More

The correlation between structure, anticloting, antithrombotic and hemorrhagic activities of heparin, heparan sulfate, low molecular weight heparins and heparin-like compounds from various sources that are in used in clinical practice or under development is briefly reviewed. Heparin-like molecules composed exclusively of iduronic acid 2-O-sulfate residues have weak anticloting activities, whereas molecules that conta Read More

Sulfated α-L-fucans from brown algae (also known as fucoidan) have complex and heterogeneous structures but recent studies revealed the occurrence of ordered repeat units in the sulfated fucans from several species. Even in these cases, the presence of highly branched portions and the complex distributions of sulfate and acetyl groups highlight the heterogeneity of algal fucans. Another source of sulfated α-L-fucans Read More

Ever since the introduction of low molecular weight heparins (LMWHs) for clinical use, one of the major questions raised relates to product interchangeability and the differences between each of the individual LMWH preparations. Although differences between various commercially available products have been described in terms of molecular weight profile and biologic properties, very limited information on the dire Read More

The use of heparin for the prophylaxis and treatment of venous and arterial thrombosis had been the standard of care for clinicians until 1982. At that time the introduction of depolymerized heparin for the prophylaxis of deep vein thrombosis in surgical patients was introduced. A number of such products, low molecular weight heparins (LMWH) were patented and introduced as new drugs during the ensuing of 20 years. Each Read More

Virtual screening, especially the structure-based virtual screening, has emerged as a reliable, cost-effective and time-saving technique for the discovery of lead compounds. Here, the basic ideas and computational tools for virtual screening have been briefly introduced, and emphasis is placed on aspects of recent development of docking-based virtual screening, scoring functions in molecular docking and ADME/Tox-base Read More

The enhancement of GABA-mediated synaptic transmission underlies the pharmacotherapy of various neurological diseases. GABAA receptors are thus targets for neuroactive drugs, including classical benzodiazepines, mediating their anxiolytic, hypnotic and anticonvulsant effects via the benzodiazepine site (BZS). Based on findings that low intrinsic efficacy and subtype selectivity can greatly improve the specificity of drug Read More

Chemokine receptors belong to the transmembrane G protein coupled receptor (GPCR) family. Although a major physiological role of chemokine receptors is for host defense by recruitment of lymphocytes to inflammatory sites, they are now found to be involved in more processes such as virus infection, tumor genesis and metastasis, and embryologic development. In this review, we show an overall picture of chemokine re Read More

Toxins have been important tools to characterize the structures and functions of K+ channels in recent years due to their unique blockage of the K+ current and other physiological functions to the K+ channels, especially the voltagegated K+ channels. Knowledge of the interacting surfaces between the toxins and the channels has been accumulated both from biological explorations and theoretical simulations. It has been fo Read More