Current Topics in Medicinal Chemistry - Volume 13, Issue 10, 2013

In drug design and enzyme engineering, the information of interactions between receptors and ligands is crucially important. In many cases, the protein structures and drug-target complex structures are determined by a delicate balance of several weak molecular interaction types. Among these interaction forces several unconventional interactions play important roles, however, less familiar for researchers. The cation-π in Read More

Transmissible spongiform encephalopathies (TSEs) are prion protein misfolding diseases that involve the accumulation of an abnormal β-sheet-rich prion protein aggregated form (PrPsc) of the normal α- helix-rich prion protein (PrPc) within the central nervous system (CNS) and other organs. On account of its large size and insolubility properties, characterization of PrPsc is quite difficult. A soluble intermediate, called PrPβ or βo, e Read More

Members of the 17β-hydroxysteroid dehydrogenase (17β-HSD) superfamily perform distinct multiple catalyses by the same enzyme, apparently contradictory to the long-held beliefs regarding the high specificity of enzymes. Surprisingly, these multi-catalyses can combine synergistically in vitro and in vivo and their dysfunction may result in the stimulation of breast or prostate cancer. 17β-HSD1 possesses high estrogen acti Read More

Despite the tremendous progress in the field of drug designing, discovering a new drug molecule is still a challenging task. Drug discovery and development is a costly, time consuming and complex process that requires millions of dollar and 10-15 years to bring new drug molecules in the market. This huge investment and long-term process are attributed to high failure rate, complexity of the problem and strict regulatory Read More

Nuclear receptors (NRs) are members of a large superfamily of evolutionarily related DNA-binding transcription factors. They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. As nuclear receptors bind small molecules that can easily be modified by drug design, and control functions associated with major diseases (e.g. cancer, osteoporosis and diabetes), they are promising phar Read More

Small molecules are involved in metabolic pathways responsible for many biological activities. Therefore it is essential to study them to uncover the unknown biological function of highly complex living systems. It is a crucial step in modern drug discovery to correctly and effectively discover small molecules’ biological function since small molecules are related to many protein functions and biological processes. This paper presents Read More

The human angiontensin-converting enzyme I (hACEI) is a zinc metalloproteinase that hydrolytically cleaves a C-terminal dipeptide from a wide range of peptide substrates, and it plays an important role in regulating blood pressure. MD simulations and interaction energy calculations for docking and crystal structures were performed to investigate the correct conformation of the ACE with enalaprilat and nanopepetide. T Read More

Human carboxylesterase I (hCES 1) plays an important role in the metabolism and activation of prodrugs, such as, the hydrolysis of a variety of drugs of prodrugs featuring an ester, amide or carbamate function. The bindings of the substrates of different lengths and cocaine to hCES1 at two different binding sites, catalytic site and Z-site, were studies through MD simulations. For each case, the correlation analysis has been pe Read More

Sucrose hydrolytic enzymes, widely used in a variety of food industries, employ sucrose as a substrate. In addition to their hydrolysis activities, they have other recently discovered characteristics that should make them useful for medical applications. Here, the two enzymes sucrose phosphorylase and invertase are discussed. Sucrose phosphorylase glycosylates non-carbohydrate small molecules and invertase can b Read More

Owing to their ability in destroying or slowing down the growth of bacteria, antibiotics have been widely used to treat the bacterial infections. However, because of the long-term and irresponsible use of antibiotics, resistance to antibiotics has become a serious problem directly threatening the public health worldwide. To fight against and resist β- lactam antibiotics, bacteria usually employed β-lactamases, especially the met Read More