The present book entitled "Novel Frontiers in the Production of Compounds for Biomedical Uses" can perhaps be placed in its best perspective by the Shakespearean character in The Tempest who exclaimed" What's past is prologue". Indeed, this compilation of some of the outstanding presentations in the field of biomedicine made at th the 9 European Congress on Biotechnology (Brussels, Belgium, July 11-15, 1999) not only reflects the achievements of the recent past, but provides a privileged glimpse of the biotechnology that is emerging in the first decade of the new Millennium. It is becoming increasingly apparent that biotechnology is offering biomedicine novel approaches and solutions to develop a sorely needed new generation of biopharmaceuticals. This is all the more necessary because in recent years, new diseases have emerged with extraordinary lethality in all corners of the globe, while age-related chronic illnesses have filled the gap wherever biomedicine has made successful inroads. The rise of antibiotic resistance also poses major threats to public health. Thus, as disease patterns evolve, the rational development of new drugs is becoming urgent, not only for the clinical outcome of patients, but also in optimising the allocation of scarce health care resources through the use of cost-effective productions methods. It is in response to all these challenges that biotechnology offers new strategies that go beyond the more traditional approaches. By the mid-1990's, the number of recombinant products approved annually for therapeutic use reached double digits. With the advent of the genomics revolution.

Nearly three thousand papers and patents are dedicated to the actual or potential uses of cyclodextrins in pharmacy and pharmaceutical formulations. This is the first book written for pharmacists and pharmaceutical technologists which not only critically summarizes the enormous amount of literature available, but which can be used as a handbook when looking for solutions to practical problems. The fundamentals -- chemistry of cyclodextrins and their derivatives -- their physical and chemical properties are condensed to the most relevant items in Chapters 1 and 2. Chapter 3 deals with the adsorption, metabolism and toxicological properties of cyclodextrins. Chapter 4 explains the formulation, structure, composition and advantageous effects of the cyclodextrin inclusion complexes. Chapter 5 describes the methods for preparation and characterization of drug/cyclodextrin complexes. Chapters 6 and 7 are dedicated to the pharmacokinetics, biopharmaceutical and technological aspects of drug/CD complexes. Chapter 8 treats the application and effects of cyclodextrins in various drug formulations. The Appendix comprises a collection of recipes for any type of drug formulation. This book is aimed at those who use cyclodextrins in drug formulations, to improve the properties of existing drug formulations, or who want to prepare quite new formulations.

A collection of readily reproducible bioinformatic methods to advance the drug discovery process from gene identification to protein modeling to the identification of specific drug candidates. The authors demonstrate these techniques, including microarray analysis, the analysis of genes as potential drug targets, virtual screening and in silico protein design, and cheminformatics, in a variety of practical situations. Because these technologies are still emergent, each chapter contains an extended introduction that explains the theory and application of the technology and techniques described.

In spite of important advances in asymmetric synthesis, chiral compounds cannot all be obtained in a pure state by asymmetric synthesis. As a result, enantiomer separation remains an important technique for obtaining optically active materials. Although asymmetric synthesis is a once-only procedure, an enantiomer separation process can be repeated until the optically pure sample is obtained. This book discusses several new enantiomer separation methods using modern techniques developed by experts in the field. These methods consist mainly of the following three types: 1) Enantiomer separation by inclusion complexation with a chiral host compound 2) Enantiomer separation using biological methods 3) Enantiomer separation by HPLC chromatography using a column containing a chiral stationary phase. Separation of a racemic compound has been called "optical resolution" or simply "resolution." Nowadays, the descriptions "enantiomer resolution" or "enantiomer separation" are also commonly used. Accordingly, "Enantiomer Separation" is used in the title of this book. The editor and all chapter contributors hope that this book is helpful for scientists and engineers working in this field.

Application of polymers from renewable resources - also identified as biopolymers - has a large potential market due to the current emphasis on sustainable technology. For optimal R&D achievements and hence benefits from these market opportunities, it is essential to combine the expertise available in the vast range ofdifferent disciplines in biopolymer science and technology. The International Centre of Biopolymer Technology - ICBT - has been created with support from the European Commission to facilitate co operation and the exchange of scientific knowledge between industries, universities and other research groups. One of the activities to reach these objectives, is the organisation ofa conference on Biopolymer Technology. In September 1999, the first international conference on Biopolymer Technology was held in Coimbra, Portugal. Because of its success - both scientifically and socially - and because ofthe many contacts that resulted in exchange missions or other ICBT activities, it was concluded that a second conference on Biopolymer Technology was justified. This second conference was held in Ischia, Italy in October 2000. And again, the scientific programme contained a broad spectrum ofpresentations in a range of fields such as biopolymer synthesis, modification, technology, applications, material testing and analytical methods."

This lab manual guides chemists through demonstrations of synergistic effects between polyelectrolytes and nanoparticles. After a short introduction into the field of polyelectrolytes and polyelectrolyte characterization, the book discusses the role of polyelectrolytes in the process of nanoparticle formation. The book also explains methods for characterization of the polyelectrolyte-modified nanoparticles.

This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans methylation inhibitors (Section E)."

1 T.J. Deming: Polypeptide and Polypeptide Hybrid Copolymer Synthesis via NCA Polymerization.- D.W.P.M. Loewik, L. Ayres, J.M. Smeenk, J.C.M. van Hest: Synthesis of Bio-inspired Hybrid Polymers Using Peptide Synthesis and Protein Engineering.- 3 H. Schlaad: Solution Properties of Polypeptide-Based Copolymers.- 4 H.-A. Klok, S. Lecommandoux: Solid State Structure, Organization and Properties of Peptide -Synthetic Hybrid Block Copolymers.- 5 K. Osada, K. Kataoka: Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers.-

The herbai medicine industry is growing at an astounding rate. Trade group estimates suggest that total sales exceeded $4 billion dollars in 1999. Herbai remedies are for sale not just in health food stores, but in supermar kets, drug stores, and even discount warehouses. Along with the proliferation in sales has come a proliferation ofinformation sources. Not all ofthe sources are equally reliable, or even intelligible. Traditional herbalists c1assify thistle and mugwort as "cholagogues," substances used to make the gallbladder con tract and release bile. Medical school graduates are unlikely to have ever heard the term, or even accept the notion that most right-sided abdominal pain is a result of diminished bile flow. Heroin and cocaine may not be the only drugs to come from plants, but a practicing physician or toxicologist might be forgiven for thinking so. In 1998, 1264 papers were published about cocaine and only 17 about kava kava, an abused herb that is not without toxic side effects. Unfortunately, the majority of the papers about kava kava were published in journals not found in ordi nary hospitallibraries. In recognition ofthis fact, and ofthe obvious need for a reliable reference work on herbai toxicology, The Toxicology and Clinical Pharmacology 0/ Herbal Products was an early addition to our new series in Forensie Science and Medicine. It is very badly needed."

An authoritative review of the current state-of-the-art understanding of the structure and function of the adrenergic receptor subtypes, as well as of the role played by these receptors in physiological and pathophysiological settings. Topics range from structure-function studies and the imaging of adrenergic receptors to the use of genetically altered mouse models and pharmacogenomics. Highlights include a survey of the knockout and overexpressed mouse models, a review of the new ways that adrenergic receptors can signal, and the effects of polymorphisms on clinical outcomes and on potential gene therapy applications. The side-by-side comparison of all the adrenergic receptors (a1, a2, and b) provides the reader with an excellent survey of the field, including the rationale for designing better drugs to control blood pressure and heart function.

An authoritative and up-to-date survey of the fundamental principles, and practice of drug delivery at the cellular level. On the principles side, the authors discuss the broad spectrum of cellular delivery, ranging from coverage of cell-mediated immunity, gene delivery, and protein targeting, to cellular drug transport, cellular drug permeability, and a variety of carrier system related to targeted drug delivery. On the practice side, the authors focus on technological developments in cellular drug delivery, including novel formulations for the delivery of DNA and antisense oligonucleotides, as well as drug targeting with immunoglobulin formulations and antibody-mediated approaches.

The endothelins are a remarkable family of signaling peptides: molecular biology predicted the existence of their receptors and synthetic enzymes prior to both the identification of the encoded proteins and the synthesis of antagonists and inhibitors for use as pharmacological tools. Although considerable advances have been made, culminating in the design of endothelin antagonists with the- peutic potential in cardiovascular disease, much remains to be discovered. Tantalizingly, new research frontiers are emerging. To support further progress, Peptide Research Protocols: Endothelin encompasses experimental protocols that interrogate all facets of an endogenous mammalian peptide s- tem, from peptide and receptor expression through synthetic pathway to peptide function and potential role in human disease. Chapters describe the use of molecular techniques to quantify the expression of mRNA for both endothelin receptors and the endothelin-converting enzymes. Peptides, precursors, receptors, and synthetic enzymes may be localized and quantified in plasma, culture supernatants, tissue homogenates, and tissue s- tions using antibodies, while additional information on receptor characterization may be obtained using radioligand binding techniques. Several protocols cover in vitro assays that determine the function of the endothelin peptides in isolated preparations, that characterize new endothelin receptor ligands, or provide inf- mation on the tissue-specific processing of endothelin precursor peptides.

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

In vitro utilization of liposomes is now recognized as a powerful tool in many bioscience investigations and their associated clinical studies, e.g., liposomes in drug targeting; liposomes in gene transport across plasma and nuclear membranes; liposomes in enzyme therapy in patients with genetic disorders. However, before these areas can be effectively explored, many basic areas in liposome research require elucidation, including: (a) attachment of liposomes to cell surfaces; (b) permeation of liposomes through the plasma membranes; and (c) stability of liposomes in cell or nuclear matrices. None of these areas have been exhaustively explored and liposome researchers have ample opportunities to contribute to our knowledge. The aim of Liposome Methods and Protocols is to bring together a wide range of detailed laboratory protocols covering different aspects of liposome biology in order to assist researchers in those rapidly advancing medical fields mentioned earlier. With this goal in mind, in each protocol chapter we have detailed the materials to be used, followed by a step-by-step protocol. The Notes section of each protocol is also certain to prove particularly useful, since the authors include troubleshooting tips straight from their benchtops, valuable information that is seldom given in restricted methods sections of standard research journals. For this reason we feel that the book will prove especially useful for all researchers in the liposome field.

A compendium of proven experimental approaches and strategies for studying the bioactivation, detoxification, tissue distribution, and elimination of xenobiotics in the metabolism and/or transport of various chemicals. The authors address several of the major drug metabolizing systems, including the cytochrome P450 family, flavin-containing monooxygenases, glutathione, S-transferase, glucuronidation, N-acetylation, and sulfotransferases. Additional chapters present novel approaches to the study of: signaling pathways in the regulation of drug metabolism enzymes, how the modulation of thiols and other low molecular-weight cofactors can alter drug metabolism, and how modulation of drug metabolism pathways can influence antiviral therapy.

Computational molecular and materials modeling has emerged to deliver solid technological impacts in the chemical, pharmaceutical, and materials industries. It is not the all-predictive science fiction that discouraged early adopters in the 1980s. Rather, it is proving a valuable aid to designing and developing new products and processes. People create, not computers, and these tools give them qualitative relations and quantitative properties that they need to make creative decisions.
With detailed analysis and examples from around the world, Applying Molecular and Materials Modeling describes the science, applications, and infrastructures that have proven successful. Computational quantum chemistry, molecular simulations, informatics, desktop graphics, and high-performance computing all play important roles. At the same time, the best technology requires the right practitioners, the right organizational structures, and - most of all - a clearly understood blend of imagination and realism that propels technological advances. This book is itself a powerful tool to help scientists, engineers, and managers understand and take advantage of these advances.

This book describes some of the most exciting developments for the discovery of new drugs, such as Fragment-based methods. It contains the latest developments in technologies that can be used to obtain the 3-D structures. This book includes experimental approaches using X-ray crystallography and NMR for Fragment-based screening as well as other biophysical methods for studying protein/ligand interactions.

Nanobiotechnology is one of the key technologies of the 21st century. It is a combination of nanoscience and biotechnology and covers areas ranging from gene transfer and nanoencapsulation to food technology. Nanocarriers are a leading nanobiotechnology tool with the ability to provide protection, site-specific delivery, enhanced bioavailability and controlled release of pharmaceuticals, genetic material, imaging agents, nutraceuticals and cosmetics to name a few. For this reason, the study of nanocarriers, their properties and applications has attracted a great deal of interest over recent years. Designed as an advanced survey of the field, this book describes the key research parameters of nanocarrier technologies including their preparation methods, evaluation of their safety and efficiency, their interaction with biologicals and their application in biotechnology, drug delivery, gene therapy and food technology areas.

B. Basler, S. Brandes, A. Spiegel and T. Bach: Total Synthesis of Kalsoene and Preussin .- R. Bandichhor, B. Nosse and O. Reiser: Paraconic Acids- the Natural Products from Lichen Symbiont .- M. Hiersemann and H. Helmboldt: Recent Progress in the Total Synthesis of Dolabellane and Dolastane Diterpenes .- L. Wessjohann and E. Ruijter: Strategies for Total and Diversity-Oriented Synthesis of Natural Product (-Like) Macrolides .- M. Sefkow: Enantioselective Synthesis of C(8)-Hydroxylated Lignans: Early Approaches and Recent Advances

This book on medicinal plant biotechnology covers recent developments in this field. It includes a comprehensive up-to-date survey on established medicinal plants and on molecules which gained importance in recent years. No recently published book has covered these carefully selected topics. The contributing scientists have been selected on the basis of their involvement in the related plant material as evident by their internationally recognised published work.

This book evolved from a graduate course on applications of statistical thermody- namics to biochemical systems. Most of the published papers and books on this subject used in the course were written by experimentalists who adopted the phenomenological approach to describe and interpret their results. Two outstanding papers that impressed me deeply were the c1assical papers by Monod, Changeux, and Jacob (1963) and Monod, Wyman, and Changeux (1965), where the allosteric model for regulatory enzymes was introduced. Reading through them I feIt as if they were revealing one of the c1everest and most intricate tricks of nature to regulate biochemical processes. In 1985 I was glad to see T. L. HilI's volume entitled Cooperativity Theory in Biochemistry, Steady State and Equilibrium Systems. This was the fIrst book to systematically develop the molecular or statistical mechanical approach to binding systems. HilI demonstrated how and why the molecular approach is so advanta- geous relative to the prevalent phenomenological approach of that time. On page 58 he wrote the following (my italics): The naturalness of Gibbs' grand partition function for binding problems in biology is evidenced by the rediscovery of what is essentially the grand partition function for this particular type of problem by various physical biochentists, including E. Q. Adams, G.

Resorcinol chemistry has been providing valuable properties and products in the development of advanced technologies in the areas of pharmaceuticals, rubber compounds, wood composites and plastics. Notable technologies include steel belted radial tires, resorcinol-formaldehyde-latex adhesives (RFL), a weather proof polycarbonate (Sollx), a super heat resistant polymer (PEN-RTM), the world's strongest fiber (Zylon), sun screens (UV absorbers), Intal (an asthma drug), Ostivone (an osteoporosis drug), Throat Plus (lozenges), Centron and Saheli (oral contraceptive pills), and many more. This new resorcinol book contains information on the chemistry and technologies developed for the usefulness of human needs. Scientists and researchers around the world working in the areas of pharmaceuticals, rubber compounds (tires, hoses, belts), polymers, polymer additives (UV absorbers, flame retardants), composites (polymers and wood), photoresists, or just simply organic chemistry will benefit from this key resorcinol reference.

Expert researchers and physician/clinicians describe in detail the newest and most commonly used technologies today in this rapidly advancing field. The authors provide readily reproducible methods for assessing the functional consequences of a certain polymorphism, evaluate the variety of genotyping platforms currently available, and discuss the management of pharmacogenomic information. Highlights include techniques for making a snapshot of the allele-specific variation in human gene expression, genome wide analysis of allele-specific expression using oligo microarrays, in vivo assays with HaploChIP, SNP genotyping in DNA pools, and PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base. The methodologies for genotyping include denaturing high-performance liquid chromarography, pyrosequencing, kinetic-fluorescence detection, mass spectrometry, and TaqMan assay for insertion/deletions.

Leading experts survey the currently available technologies designed to improve the delivery of today's cancer chemotherapeutic agents. The authors review both the theoretical and practical considerations governing conventional and nonconventional methods of drug administration, and identify promising opportunities for product development. In their outline and discussion of the use of novel formulation technologies-including synthetic polymers and biomaterials for prolonged or sustained drug release to achieve potentially greater therapeutic effect-they profile those technologies that have resulted in a number of approved and late-stage clinical products.