In this thesis, the author investigates the chemistry and application of molecules containing urea and amide bonds. These bonds are some of the strongest known and are fundamental to biological processes. The author describes his discovery that sterically hindered ureas undergo solvolysis at room temperature under neutral conditions. This is a remarkable finding, since ureas are inert under these conditions and a general rule of chemistry is that hindered substrates are less reactive. Remarkably, the author translates these results to the correspondingly sterically hindered amides. This thesis has resulted in a number of outstanding publications in high profile journals. The unique method for breaking urea and amide bonds developed in this study is likely to have far reaching consequences for biological protein manipulation.

Part II of this excellent work covers proteoglycans and mucins and deals with many more examples of glycoprotein function. It also covers glycoproteins from four more species (slime mold, snails, fish, batracians).

The content of the volume is very comprehensive in that most contributors are focussed on discussing, in depth, the wealth of most recent advances in their field, referring to previous reviews of older work for background information. This method effectively produces a very wide subject coverage in a smaller number of chapters/volumes.

The volume is an important information source for all glycobiologist researchers (senior investigators, post-doctoral fellows and graduate students), and as a good, comprehensive, reference text for scientists working in the life sciences.

During the course of evolution, an imbalance was created between the rate of vertebrate genetic adaptation and that of the lower forms of living organisms, such as bacteria and viruses. This imbalance has given the latter the advantage of generating, relatively quickly, molecules with unexpected structures and features that carry a threat to vertebrates. To compensate for their weakness, vertebrates have accelerated their own evolutionary processes, not at the level of whole organism, but in specialized cells containing the genes that code for antibody molecules or for T-cell receptors. That is, when an immediate requirement for molecules capable of specific interactions arose, nature has preferred to speed up the mode of Darwinian evolution in pref- ence to any other approach (such as the use of X-ray diffraction studies and computergraphic analysis). Recently, Darwinian rules have been adapted for test tube research, and the concept of selecting molecules having particular characteristics from r- dom pools has been realized in the form of various chemical and biological combinatorial libraries. While working with these libraries, we noticed the interesting fact that when combinatorial libraries of oligopeptides were allowed to interact with different selector proteins, only the actual binding sites of these proteins showed binding properties, whereas the rest of the p- tein surface seemed "inert. " This seemingly common feature of protein- having no extra potential binding sites--was probably selected during evolution in order to minimize nonspecific interactions with the surrounding milieu.

Molecular modeling has undergone a remarkable transformation in the last 20 years. This book provides thorough introductions and a compilation of step-by-step methods applicable to problems faced by non-specialists especially those new to the software packages used in molecular modeling. Tips on troubleshooting and avoiding common pitfalls are included in the book, along with chapters covering a wide range of subjects. Links to downloadable software are also provided.

This volume successfully and clearly examines how biophysical approaches can be used to study complex systems of reversibly interacting proteins. It deals with the methodology behind the research and shows how to synergistically incorporate several methodologies for use. Each chapter treats and introduces the reader to different biological systems, includes a brief summary of the physical principles, and mentions practical requirements.

Humans have been "manually" extracting patterns from data for centuries, but the increasing volume of data in modern times has called for more automatic approaches. Early methods of identifying patterns in data include Bayes' theorem (1700s) and Regression analysis (1800s). The proliferation, ubiquity and incre- ing power of computer technology has increased data collection and storage. As data sets have grown in size and complexity, direct hands-on data analysis has - creasingly been augmented with indirect, automatic data processing. Data mining has been developed as the tool for extracting hidden patterns from data, by using computing power and applying new techniques and methodologies for knowledge discovery. This has been aided by other discoveries in computer science, such as Neural networks, Clustering, Genetic algorithms (1950s), Decision trees (1960s) and Support vector machines (1980s). Data mining commonlyinvolves four classes of tasks: * Classi cation: Arranges the data into prede ned groups. For example, an e-mail program might attempt to classify an e-mail as legitimate or spam. Common algorithmsinclude Nearest neighbor,Naive Bayes classi er and Neural network. * Clustering: Is like classi cation but the groups are not prede ned, so the algorithm will try to group similar items together. * Regression: Attempts to nd a function which models the data with the least error. A common method is to use Genetic Programming. * Association rule learning: Searches for relationships between variables. For example, a supermarket might gather data of what each customer buys.

Wheat is the world's most important agricultural commodity. In Europe, where wheat is the main staple, bread wheat (Triticum aestivum) covers the majority of land on which wheat is cropped. Wheat breeders and technologists have contributed greatly to the continued success of bread wheat and its products. The bread-making quality' of a wheat variety can be described in relation to the processing its kernels must undergo to make a good bread. Bread wheat kernels must be suitable for proper milling into a flour that can produce a dough capable of becoming fine bread. The type of bread varies depending on local bread-making practices. Part I of this book contains a study of the anatomy and chemical composition of wheat kernels, and of the fundamental difference between soft' and hard' kernelled varieties. It relates these characteristics to the processes of milling, dough-making and manufacturing of bread, and to biscuit and pasta making. The genetic basis for these characteristics is illustrated, and assay methods for characterizing wheat varieties - ranging from Saunders' chewing test to the most recent developments in glutenin and gliadin research - are evaluated. Part II briefly describes - country by country - how bread-making quality has been integrated into wheat-breeding programmes throughout Europe, and how breeders have attempted to resolve the conflict between yield and quality. It describes how quality wheats travelled' around the world - from their endogenic source in Eastern Europe to North America, and back again to Europe. This explains how specific genetic material can appear in the pedigrees of varieties grown in a wide range of agro-ecological zones. In addition to givingan interesting historical survey, the book points the way forward for breeders' efforts in the future. Bread-Making Quality updates and interprets knowledge in a way that makes it particularly accessible for food technologists, breeders, students, and teachers.

A readily reproducible collection of established and emerging techniques for studying the interaction between proteins and ligands, including biochemical/bulk techniques, structure analysis, spectroscopy, single-molecule studies, and theoretical/computational tools. Among the highlights are surface plasmon resonance (SPR) and reflectometric biosensor approaches, high-throughput screening with confocal optics microscopy, single molecule fluorescence and fluorescence correlation spectroscopy (FCS), atomic force microscopy (AFM), crystallography of reaction intermediates, and time-resolved x-ray crystallography. The protocols follow the successful Methods in Molecular Biologya"[ series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.

A wealth of information has accumulated over the last few years on the human genome. The new insights have completely changed the focus of protein analysis. It is no longer time-consuming analysis of unknown products, but rather selective identifications of individual forms, modifications and processings, and overall analysis of global protein outputs from cells and tissues in health and disease. This book gears to the rising need of sensitive, accurate, and fast separation and identification techniques in proteomics. It discusses current methodologies of modern protein analysis, from isolation and sample preparation, over analysis and identification, to final characterization. Several evaluations concentrate on the now productive approaches of two-dimensional gel electrophoresis and mass spectrometry, but alternative methods and further perspectives are also outlined. The book includes an overlook over current databases to connect protein analysis data with all available information, ...

Neuropeptide Y (NPY) is a ubiquitous and important messenger in the nervous system, with a wide range of physiological roles. It is involved in the body energy balance and is one of the most potent stimuli of food intake known. NPY also acts to regulate central and peripheral autonomic functions.
This book, written by academic and industrial experts in the field, links the most recent basic experimental knowledge about NPY and its receptors with areas of clinical importance.
This book will be of interest to those working in all areas of research affected by NPY, such as food intake and energy homeostasis, cardiovascular regulation and G-protein-coupled receptors, as well as those interested in the development of drugs as NPY targets.
Key Features
* The hypothalamic role of NPY and its relationship with eating disorders and diabetes
* The sympathetic nervous system role of NPY and its involvement in cardiovascular disorders
* Characterization of NPY receptor types and their brain distribution, molecular biology and pharmacology
* Development of peptide and non-peptide receptor antagonists

This detailed volume explores advances in vector design, DNA delivery, cell cultivation, host cell engineering, and bioprocess optimization within the study of recombinant protein expression in mammalian cells. The majority of the protocols employ either Chinese hamster ovary cells (CHO) or human embryonic kidney 293 cells (HEK293), the workhorses of the field, as the production host; however, the methods can be adapted to other mammalian hosts under the appropriate cell-specific conditions. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and convenient, Recombinant Protein Expression in Mammalian Cells: Methods and Protocols aims to aid researchers in building on our knowledge of protein structure and function and to speed the discovery of new therapeutic proteins.

Glutamate is the major excitatory neurotransmitter in the brain and dysfunction of glutamate transmission is the likely cause of a variety of diseases including neurodegeneration following cerebral ischemia, Huntington's chorea, amyotrophic lateral sclerosis, epilepsy, spasticity, emesis, chronic pain, and schizophrenia. Excitatory amino acid receptor agonists and antagonists are therefore of major interest as potential drugs for central nervous system disorders. Excitatory Amino Acids is the first book entirely dedicated to the results of human testing of modulators of excitatory amino acid neurotransmitters.
Features include:
* Coverage of the field of excitatory amino acids from synaptic function to preclinical and clinical pharmacology
* Description of the development of NMDA ("N"methyl-"d"-aspartate) and non-NMDA antagonists
* Reports of potential drugs in early and late clinical stages of development.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 90 years The Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic, and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

Techniques in Protein Chemistry VII, a valuable bench-top reference tool for protein chemists, features the most up-to-date advances in protein methodologies.
Key Features
* Protein sequencing and amino acid analysis
* Mass spectral analysis of peptides and proteins
* Posttranslational processing
* High-sensitivity protein and peptide separations
* Protein folding and NMR
* Functional domain analysis
* Protein design and engineering

Amyloid diseases are characterized by the deposition of insoluble fibrous amyloid proteins. The word "amyloid" indicates a starch-like compound, and though a misnomer, continues to be the accepted term for this group of protein conformational disorders. The second edition of Amyloid Proteins expands upon the previous edition with current, detailed protocols for the preparation of amyloid and its precursors, specific analytical methods for studying these proteins, cell culture models and assays for production of amyloid proteins, and protocols for amyloid extraction from tissue, its detection in vitro and in vivo, as well as nontransgenic methods for developing amyloid mouse models. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Amyloid Proteins, Second Edition seeks to aid scientists in the amyloid field to establish new techniques in their laboratories. Authoritative and practical, Amyloid Proteins, Second Edition seeks to aid scientists in the amyloid field to establish new techniques in their laboratories.

This important volume is mainly concerned with the development of methods for "sequencing" - that is, determination of the order of the amino acids in proteins and of nucleotides in RNA and DNA. In 1943 the position of only one amino acid in a protein (insulin) was known, and Sanger's first paper resulted in finding a second amino acid. In his final paper in 1982 he describes the determination of a DNA sequence of 48,502 nucleotides. The papers describe the steady improvements in techniques, and exciting biological results revealed by the sequences.

The elucidation during the latter half of the 20th century of the mechanisms by which information flows from nucleic acids to proteins has completely changed the face of biological research. Many diseases are caused by abnormalities in control mechanisms which are not immediately essential for life itself but which maintain the normal social behavior of differentiated cells in multicellular organisms. The complex sugar chains of glycoproteins and glycolipids are believed to play important roles in the control of cellular functions and in recognition between the cell and its cellular and fluid environment. Investigations into the abnormalities of complex sugar chain assembly are expected to yield an important new underatanding of the etiology and pathogenesis of human diseases. This volume discusses several representative diseases which emphasize the current status of glycopathology, and will stimulate further research in this exciting field.

In Protein Structure, Stability, and Folding, Kenneth P. Murphy and a panel of internationally recognized investigators describe some of the newest experimental and theoretical methods for investigating these critical events and processes. Among the techniques discussed are the many methods for calculating many of protein stability and dynamics from knowledge of the structure, and for performing molecular dynamics simulations of protein unfolding. New experimental approaches presented include the use of co-solvents, novel applications of hydrogen exchange techniques, temperature-jump methods for looking at folding events, and new strategies for mutagenesis experiments. Unique in its powerful combination of theory and practice, Protein Structure, Stability, and Folding offers protein and biophysical chemists the means to gain a more comprehensive understanding of some of this complex area by detailing many of the major techniques in use today.

The G proteins are a family of structurally homologous, plasma membrane-associated guanine-nucleotide-binding proteins. These proteins play an integral role in the tra- duction of extracellular signals through second messenger systems. As such, G proteins affect a wide variety of intra cellular biochemical reactions by regulating the concent- tion of second messengers in cells. G proteins are heterotrimeric, consisting of a, p, and y polypeptide chains, with G protein specificity largely det- mined by the a-subunit, Molecular cloning of G protein s- units has revealed 23 distinct a-subunits, encoded by 17 different genes. Based on functional measures, G proteins are generally classified into three major categories: the G, family, which is stimulatory for adenylyl cyclase; the G, f- ily, which is inhibitory for adenylyl cyclase; and the G, f- ily, which stimulates phospholipases (Birnbaumer and Birnbaumer, 1995). Alternatively, on the basis of sequence homology, G proteins can be subdivided into four cate- ries: G,, G,, G,, and G12.

In recent years, research has shown the importance of peptides in neuroscience, immunology, and cell biology. Active research programs worldwide are now engaged in developing peptide-based drugs and vaccines using modification of natural peptides and proteins, design of artificial peptides and peptide mimetics, and screening of peptide and phage libraries.
In this comprehensive book, the authors discuss peptide synthesis and application within the context of their increasing importance to the pharmaceutical industry. Peptides: Synthesis, Structures, and Applications explores the broad growth of information in modern peptide synthetic methods and the structure-activity relationships of synthetic polypeptides.
Coverage includes:
* The history of peptide chemistry
* Amide formation, deprotection, and disulfide formation in peptide synthesis
* Solid-phase peptide synthesis
* a-helix formation by peptides in water
* Stability and dynamics of peptide conformation
* An overview of structure-function studies of peptide hormones
* Neuropeptides: peptide and nonpeptide analogs
* Reversible inhibitors of serine proteinases
* Design of polypeptides
* Current capabilities and future possibilities of soluble chemical combinatorial libraries
* Epitope mapping with peptides
* Synthesis and applications of branched peptides in immunological methods and vaccines

"Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC): Methods and ""Protocols "provides a synopsis of a large array of different SILAC methods by presenting a set of protocols that have been established by renowned scientists and their working groups. These include methods and protocols for the labeling of various model organisms as well as advanced strategies relying on SILAC, e.g. for the analysis of protein interactions, the mapping of posttranslational modifications or the characterization of subcellular proteomes. Written in the highly successful "Methods in Molecular Biology "series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, "Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC): ""Methods and Protocols "will serve students and experienced scientists alike as a valuable reference of how to make use of the SILAC technology for their own research.

The discovery of microRNAs and its role as gene expression regulators in human carcinogenesis represents one of the most important scientific achievements of the last decade. More recently, other non-coding RNAs have been discovered and its implications in cancer are emerging as well, suggesting a broader than anticipated involvement of the non-coding genome in cancer. Moreover, completely new and unexpected functions for microRNAs are being revealed, leading to the identification of new anticancer molecular targets. This book represents a comprehensive guide on non-coding RNAs and cancer, spanning from its role as cancer biomarkers, to providing the most useful bioinformatic tools, to presenting some of the most relevant discoveries, which indicates how these fascinating molecules act as fine orchestrators of cancer biology.

Glycosylation is the most abundant post-translational modification of proteins. Estimates vary widely, but a common assessment is that upwards of 50% of eukaryotic proteins are modified by some type of glycan. In Mass Spectrometry of Glycoproteins: Methods and Protocols, expert researchers in the field detail many of the methods that are now commonly used for glycoproteomics. These methods and techniques include robust sample preparation techniques; advanced chromatographic strategies for improving dynamic range; state-of-the-art mass spectrometry instrumentation and associated ionization and fragmentation methods; and informatics tools used for identifying glycoproteins and characterizing the associated glycans. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Mass Spectrometry of Glycoproteins: Methods and Protocol is an essential resource for those who work at the interface of glycobiology and mass spectrometry.

The Fifth Chinese Peptide Symposium, hosted by Lanzhou University, was held at Lanzhou, China July 14-17, 1998, with 156 participants, including 30 scientists from abroad, representing nine countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-98 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 8 sessions with 42 oral and 90 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistry-biology-interface and challenging problems in peptides. The enthusiastic cooperation and excellent contributions were gratifying and the active response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. Kit Lam of the University of Arizona and Dr. Yun-Hua Ye of Peking University were the recipients of "The Cathay Award" sponsored by the H. H. Liu Education Foundation, offered for their seminal contribution in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group).

This detailed volume encompasses chapters from leading experts in the area of membrane proteins who describe step-by-step protocols developed these last few years to improve the functional production and stabilization of recombinant integral membrane proteins (IMPs). Membrane proteins play a key role in numerous pathologies such as cancer, cystic fibrosis, epilepsy, hyperinsulinism, and Alzheimer's disease, yet studies on these and other disorders are hampered by a lack of information about the proteins involved. This book sets out to aid researchers in rectifying this situation. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Heterologous Expression of Membrane Proteins: Methods and Protocols, Second Edition serves as an ideal guide for scientists attempting to delve deeper into the myriad unique IMP structures.