Current Medicinal Chemistry - Volume 11, Issue 8, 2004

Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic sidechain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In th Read More

Human Urotensin-II is a potent vasoconstrictor and binds with high affinity to GPR14 receptor, recently cloned and renamed UT receptor. U-II vasoconstrictive potency is reported to be an order of magnitude greater than that of endothelin-1 (ET-1), which would make it the most potent mammalian vasoconstrictor identified to date. Urotensin-II is a neuropeptide “somatostatin-like” cyclic peptide, which was originally isola Read More

Heme is an essential molecule with contradictory biological functions. In hemoproteins such as hemoglobin and cytochromes protein-bound heme is a prosthetic group serving physiological functions as a transporter for oxygen and electrons. On the other hand free heme can have deleterious effects by generating reactive oxygen species that cause oxidative stress. Consequently, heme homeostasis of the cell must be tightly c Read More

The central cholinergic system and muscarinic cholinergic receptor (mR) activation have long been associated with cognitive function. And degeneration of the cholinergic basal forebrain (CBF) neurons is a pronounced hallmark of Alzheimer's Disease (AD). However, CBF immunolesions as animal models of AD cholinergic degeneration have not replicated the robust memory deficits of nonselective excitotoxic lesions. The Read More

The well known calcium-sensitive phosphatase calcineurin is implicated in many eukaryotic activation and developmental programmes, including lymphocyte activation, heart-valve morphogenesis, angiogenesis, and neural and muscle development. The importance of this phosphatase is graphically illustrated by the observation that the immunosuppressive actions of the microbial drugs Cyclosporin A (CsA) and FK506 aris Read More

This review traces the development of a series of potent and selective antitumour benzothiazoles from the discovery of the initial lead compound, 2-(4-amino- 3-methylphenyl)benzothiazole (DF 203) in 1995 to the identification of a clinical candidate, Phortress, scheduled to enter Phase 1 trials in Q1 2004 under the auspices of Cancer Research U.K. Advances in our understanding of the mechanism of action of this unique series Read More

DNA-protein interaction in the 5' upstream polymorphic region of the dopamine D4 receptor (DRD4) gene was analyzed by capillary electrophoretic mobility shift assay (CEMSA). The sequence of interest was amplified using a fluorescent primer and applied as a probe in the binding assays with HeLa nuclear extract. Serial dilution of the probe resulted in a concentration dependent DNA-protein complex formation. Sp 1 specific ol Read More

Apoptosis (or programmed cell death) is a genetically controlled “cell suicide” pathway which plays an essential role in deleting excess, unwanted or damaged cells during development and tissue homeostasis. Dysregulation of apoptosis contributes to a wide variety of pathological conditions, including AIDS, cardiovascular disease, infectious disease, autoimmunity and neurodegenerative disorders. Resistance to apoptosis is als Read More

Vitamin C (ASC) is well known as an outstanding antioxidant in animal tissues. This concept is reviewed from a chemical standpoint, starting from a chemical view of radical reactions in the cell. ASC, vitamin E, and lipid hydroperoxide were selected as key molecules involved in radical reactions in the cell, and their efficiencies as an index of oxidative stress were evaluated. At first, methods for specific and sensitive determination of Read More

The group of diseases caused by abnormalities of the process of protein folding and unfolding is rapidly growing and includes diseases caused by loss of function as well as diseases caused by gain of function of misfolded proteins. Amyloidoses are caused by gain of function of certain proteins that lose their native structure and self-assemble into toxic insoluble, extracellular fibrils. This process requires the contribution of multip Read More