Drug Targeting

Unlike traditional biological research that focuses on a small set of components, systems biology studies the complex interactions among a large number of genes, proteins, and other elements of biological networks and systems. Host-pathogen systems biology examines the interactions between the components of two distinct organisms: a microbial or viral pathogen and its animal host. With the availability of complete genomic sequences of a variety of hosts and pathogens, together with breakthroughs in proteomics, metabolomics, and other experimental areas, the investigation of host-pathogen systems on a multitude of levels of detail has come within reach. This chapter introduces methods and approaches for the analysis of host-pathogen systems. We will particularly emphasize the role of biochemical networks for the study of complex relationships across species boundaries. Although the research area of host-pathogen systems biology spans multiple spatial and temporal scales, we will focus on the molecular and cellular aspects of pathogen-host interactions. We will cover the construction of biochemical networks, the identification of functional response sub-networks, and their comparative network analysis. These methods find application in the identification of host markers and drug targets for further drug development and therapeutic interventions. We will also provide a brief review of other modeling techniques and applications within host-pathogen systems biology, including rule-based modeling of signal transduction pathways, immune system models, and physiological top-down approaches.

The non-neuronal cholinergic system is widely expressed in human airways. Choline acetyltransferase (ChAT) and/or acetylcholine are demonstrated in more or less all epithelial surface cells (goblet cells, ciliated cells, basal cells), submucosal glands and airway smooth muscle fibres. Acetylcholine is also demonstrated in the effector cells of the immune system (lymphocytes, macrophages, mast cells). Epithelial, endothelial and immune cells express nicotinic and muscarinic receptors. Thus the cytomolecule acetylcholine can contribute to the regulation of basic cell functions via auto-/paracrine mechanisms (proliferation, differentiation, ciliary activity, secretion of water, ions and mucus, organization of the cytoskeleton, cell-cell contact). Acetylcholine also modulates immune functions (release of cytokines; proliferation, activation and inhibition of immune cells). Preliminary experimental evidence suggests that mucosal inflammation may be associated with raised acetylcholine le...

Phospholipase A2 is potentially an important target for structure-based rational drug design. In order to determine the involvement of phospholipase A2 in the action of non-steroidal anti-inflammatory drugs (NSAIDs), the crystal structure of the complex formed between ...

Microbial biofilms have been observed as congregates and attached communities on a diverse range of microecosystems of medicinal and industrial importance. Until recently, most investigations have been performed on planktonic (floating or fluid phase) microorganisms. After realization of the biofilm existence and their recalcitrance toward conventionally adopted preventive strategies and antimicrobial agents, research has been shifted toward novel therapeutics based drug delivery and targeting approaches. With the emergence of various biofilm models and methods to assess biofilm formation and physiology, it is pivotal to discuss various novel strategies that may become the therapeutic tools and clinically adaptable strategies of the future. This review explores various novel research strategies studied to date for their potential in effective biofilm eradication.

Summary Genomics, particularly high-throughput sequencing medicine is that disease could be treated according to genetic and specific individual markers, selecting and characterization of expressed human genes, has created new opportunities for drug discovery. medications and dosages that are optimized for indi- vidual patients. The possibility of defining patient Knowledge of all the human genes and their func- tions may allow

There were 13,176 roadside drug tests performed in the first year of the random drug-testing program conducted in the state of Victoria. Drugs targeted in the testing were methamphetamines and Delta(9)-tetrahydrocannabinol (THC). On-site screening was conducted by the police using DrugWipe, while the driver was still in the vehicle and if positive, a second test on collected oral fluid, using the Rapiscan, was performed in a specially outfitted "drug bus" located adjacent to the testing area. Oral fluid on presumptive positive cases was sent to the laboratory for confirmation with limits of quantification of 5, 5, and 2 ng/mL for methamphetamine (MA), methylenedioxy-methamphetamine (MDMA), and THC, respectively. Recovery experiments conducted in the laboratory showed quantitative recovery of analytes from the collector. When oral fluid could not be collected, blood was taken from the driver and sent to the laboratory for confirmation. These roadside tests gave 313 positive...

Tumor vascular permeability factor (VPF) was initially identified by Senger et al. in the laboratory of Dvorak [1] and was later confirmed as identical to VEGF [2, 3, 4 and 5]. Although more attention has been focused on angiogenesis, the other side of biological activity of VEGF, the ...

Abstract—The first step from the scientific data to drugs, it is the identification of drug active substance candidates called "drug discovery". As technology in the medical world evolves, the use of new methods has enabled some questions to be answered. Biology has emerged from being a science field that is currently being studied only in the laboratory and has become a scientific discipline working with information technology. Bioinformatics is the process of storing and processing biological data using computers and software to respond to these biological issues. In this context, drug discovery has accelerated in the process of organizing, directing and interpreting results from biological information. In this study, it is mentioned which phases are passed through bioinformatics during the drug discovery process and which methods are used at these stages. The first step in the drug discovery process is to set an appropriate target. This can be a disease state, a molecule or protein associated with a gene. Within the context of bioinformatics information, drugs can be designed using biological data with various algorithms.

Özet—Bilimsel verilerden ilaçlara uzanan aşamalardan ilki ("drug dıscovery") yani "ilaç keşfi" olarak adlandırılan ilaç etkin madde adaylarının saptanmasıdır. Tıp dünyasındaki teknoloji geliştikçe yeni methotların kullanılması bazı soruların açıklığa çıkabilmesini sağlamıştır. Biyoloji günümüzde sadece laboratuvarda çalışılan bir bilim alanı olmaktan çıkmış ve bilgi teknolojisiyle iç içe çalışan bir bilim dalı haline gelmiştir. Biyoinformatik de bu biyolojik meselelere cevap verebilmek için bilgisayarlar ve yazılımlarının kullanılarak biyolojik verilerin depolanması ve işlenmesi süreçleridir. Bu kapsamda biyolojik bilgilerden veriyi organize etmede, yönetmede ve yorumlama sonuçlarında ilaç keşfi sürecide hız kazanmıştır. Bu çalışmada ilaç keşfi sürecinde biyoinformatik kullanılarak hangi aşamalardan geçildiğini ve bu aşamalarda hangi yöntemlerin kullanıldığına değinilmiştir. İlaç keşif işleminde ilk adım olarak, uygun bir hedef belirlemektir. Bu bir hastalık durumu, bir gen ile ilişkili bir molekül veya protein olabilir. Biyoinformatik bilgiler kapsamında da çeşitli algoritmalar ile biyolojik veriler kullanılarak ilaçlar tasarlanabilmektedir. Anahtar Kelimeler—biyoinformatik, ilaç keşfi, genomik, hedef tanımlama

There is an urgent need to develop new drugs against eukaryotic parasitic protozoa such as Plasmodium, Trypanosoma and Leishmania, which cause the diseases malaria, trypanosomiasis and the leishmaniases respectively. The biology of these organisms has many unusual facets that might be exploited for drug design, and the recent availability of parasite genome sequence data has facilitated the search for novel drug targets. Here we review current understanding of the cell cycle in these parasites and show that important structural and functional differences exist between parasite and mammalian cell cycle control machineries and signal transduction pathways, which might be utilised for rational drug design. Potential targets include protein kinases from the cyclin-dependent kinase, cAMP-dependent kinase and mitogen activated protein kinase families.