Current Medicinal Chemistry - Volume 11, Issue 20, 2004

The release of hormones is subject to a complex and finely tuned regulation system. The biosynthesis plays a key role by specifically converting the prohormone precursor into its biological active product(s). A family of mammalian proteases could be identified to be responsible for the endoproteolytic processing. These subtilisin / kexin-like prohormone convertases (PC) recognize their substrates at single or pairs of basi Read More

Persistent infection with the hepatitis B virus (HBV) represents a major health problem worldwide with over 350 million patients at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double-stranded DNA virus with four overlapping genes and a unique life cycle, creating an intracellular pool of covalently closed circular DNA molecules for persistence and an RNA template for replication via revers Read More

In recent years, the gaseous molecule nitric oxide (NO) has been shown to be involved in many important biological events. S-Nitrosothiols are biological substances derived endogenously from NO, and are found in a variety of tissues exhibiting NO-mimetic activity. Fundamental studies on the chemical aspects of S-nitrosothiols have become an integral part of NO research, with a view to further understanding the numerou Read More

Many non-cardiovascular drugs of common clinical use cause, as an unwanted accessory property, the prolongation of the cardiac repolarisation process, due to the block of the HERG (Human Ether-a-go-go Related Gene) potassium channel, responsible for the repolarising IKr current. This delayed cardiac repolarisation process can be often unmasked by a prolongation of the QT interval of the ECG. In these conditions, pre Read More

Diabetes Mellitus is by far one of the most propagated chronic diseases, affecting 150 million people worldwide. This affliction is caused by a malfunction of pancreatic endocrine cells, which provokes a failure in the insulin release and glucose homeostasis. Plasma membrane KATP channels have a key role in the stimulus-secretion coupling of pancreatic β-cells. Consequently, many investigations have developed effi Read More

Glucose transporters, or membrane proteins, which incorporate glucose into the cell, can be divided into two groups: the facilitative type glucose transporter (GLUT), and the sodium / glucose cotransporter (SGLT). Among the GLUT family isoforms, GLUT4 is particularly important for maintaining glucose metabolism homeostasis since it is involved in insulin or exercise-induced glucose transport into muscle and adipos Read More

Reversible phosphorylation of Tyr residues in proteins plays a central role in the transduction of signals. For both SH2 domains and for protein tyrosine phosphatases (PTPs) the phosphate group of phosphotyrosine (pTyr) of peptides provides a key affinity element, but its highly charged nature and its hydrolytic lability render it unsuitable in inhibitor design. The research in the recent years has been addressed to find pTyr Read More

The treatment of viral diseases remains one of the major challenges to modern medicine. During the past two decades there has been increased recognition of the consequences of serious viral illnesses that are not controlled by vaccination. These illnesses include human immunodeficiency virus, human herpes viruses, and viruses that cause hepatitis. There are now eight pathogens recognized in the herpes virus family that Read More

Advanced glycation endproducts (AGE) are a class of compounds resulting from glycation and oxidation of proteins, lipids or nucleic acids. Glycation is the non-enzymatic addition or insertion of saccharide derivatives to these molecules. This leads to the formation of intermediary Schiff bases and Amadori products and finally to irreversible AGE. This classical view has been modified in recent years with recognition of the importanc Read More