Tidak ada kategori

the classical field of medicinal chemistry has been augmented and today comprises a huge range of techniques and methodologies from QSAR and structure-based design to the recently developed ‘‘highthroughput’’ synthesis and screening. A paradigmatic change in the 1990s gave rise to a focus on the molecular level of drug action and hence demanded the development of appropriate biological assay technology. This is the point where the present book starts. In the first part, molecular targets are dealt with, going deep into cellular assay technologies. Cell-based assays imply not only the ‘‘simple’’ detection of one cellular product, but the tracking of a variety of metabolic processes, finally resulting in a multidimensional phenotypic characterization of cellular behavior. In a hierarchical step, the second chapter introduces the ‘‘gene knock-out’’ models, a technique that allows to ‘‘design’’ a disease model within a complex organism to generate a more relevant analytical tool for medicinal chemistry. The subsequent chapter deals with a fascinating readout technology for molecular assays, the socalled reporter genes. The second part of the book is devoted to synthesis. Two important fields can benefit tremendously from molecular biology and its techniques: Stereoselective synthesis of natural compounds and of their mimics, and synthesis of DNAderived drugs or protein drugs. The first chapter within this section gives a comprehensive overview about the use of enzymes in stereoselective synthesis, emphasizing recombinant technologies, which greatly enhance the selection of working tools. The fascinating field of nucleic acid drugs, the design and synthesis, their mimics and their mechanisms of action are the topics of chapter 6. The third part deals with questions of analysis. Invaluable contributions have come from use of proteins for enantioseparation and affinity chromatography. The use of NMR and associated techniques for structure elucidation is another analytical topic to read about in this section. Kinetics, metabolism, toxicology, and the very rapidly growing fields of pharmacogenomics and toxicogenomics form the contents of the final part of this book which is unique in its presentation of today’s entanglement of the biosciences with medicinal chemistry.