Combinatorial Chemistry & High Throughput Screening - Volume 8, Issue 2, 2005

High throughput screening approaches have found their way into many if not all pharmaceutical companies and have made important contributions to basic science as well as to drug development. An important aspect is that the combinatorial principle has not only been applied in molecular biology techniques, where randomized oligonucleotides have been incorporated into genes coding for phage and bacteria sur Read More

For almost 15 years phage display is being used for the selection of specific antigen-binders from artificial libraries of single chain antibodies. Filamentous phages have been developed in a way to express foreign proteins on the surface and at the same time carrying the genetic information of the surface expressed molecule within the phage capsid. This property guarantees the coupling of phenotype and genoty Read More

A multitude of systems for the presentation of foreign peptides or proteins on the surface of microorganisms has been developed within the past two decades. However, the majority of the bacterial surface display systems are devoted to the presentation of heterologous antigens to the immune system (vaccine generation). Bacteria are the preferable hosts for the generation of vast genetic repertoires, and their genetic Read More

Synthetic peptides have a long tradition as molecular tools in biomedical research and drug discovery. The introduction of high-throughput synthesis and screening technologies for synthetic peptides, such as arrays and combinatorial libraries, enabled the large-scale and detailed exploration of protein-ligand interactions, as well as the discovery of novel biologically active peptides. This review summarizes currently Read More

With the success of the human genome project, the focus of life science research has shifted to the functional and structural analyses of proteins, such as disease proteomics and structural genomics. These novel approaches to the analyses of proteins, including newly identified ones, are expected to help in the identification and development of protein therapies for various diseases. Thus, disease proteomic-based drug dis Read More

The application of combinatorial chemistry to glycobiology historically has proven challenging due to numerous synthetic hurdles. The advent of novel methodologies has enabled the production of natural as well as mimetic analogues for proof-of-concept experiments and SAR. This review highlights some of the recent synthetic advances in combinatorial carbohydrate synthesis. The application of carbohydrate libraries in gl Read More

The transmembrane metzinkin-proteases of the ADAM (a disintegrin and a metalloproteinase)-family ADAM10 and ADAM 17 are both implicated in the ectodomain shedding of various cell surface molecules including the IL6-receptor and the transmembrane chemokines CX3CL1 and CXCL16. These molecules are constitutively released from cultured cells, a process that can be rapidly enhanced by cell stimulation with phorbol Read More

Cytokines are important mediators of many cellular functions including coordination of the immune system and regulation of regenerative processes. Therefore, cytokines can be exploited for therapeutic strategies. Cytokines can be altered in a way that their biologic activity is enhanced or antagonized. This can be accomplished by changing the interaction of cytokines with their cognate cytokine receptor comp Read More

The pivotal role of kinases in signal transduction and cellular regulation has lent them considerable appeal as pharmacological targets across a broad spectrum of pathologies. Since the discovery that the v-Src oncogene encoded a protein kinase in 1978, kinases have remained a focus of research for pharmaceutical laboratories and academic groups alike. Many have sought to develop orally available low molecular weigh Read More

Proteases are key regulators of many physiological and pathological processes [1,2], and are recognized as important and tractable drug candidates. Consequently, knowledge of protease substrate recognition and specificity promotes identification of biologically relevant substrates, helps elucidating a protease's biological function, and the design of specific inhibitors. Traditional methods for establishing substrate rec Read More