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.

This volume documents this unique family of cell surface proteins. Despite masquerading as intractable and difficult to clone and characterize, ENOX proteins have and continue to offer remarkable opportunities for research, commercial development and outside confirmation of therapeutic, diagnostic and new paradigms to help explain complex biological processes.

TwentyyearshavegonebysinceJackSokatch?rstpublishedhisoutsta- ingTheBiologyofPseudomonasbackin1986.Thiswasfollowedbytwobooks published by the ASM that contained the presentations of the Pseudomonas meetings held in Chicago in 1989 and Trieste in 1991. The earlier volume of these two was edited by Simon Silver, Al Chakrabarty, Barbara Iglewski, and Sam Kaplan, and the later one by Enrica Galli, Simon Silver, and Bernard Witholt. The time was ripe for a series of books on Pseudomonas because of its importance in human and plant pathogenesis, bio?lms, soil and rhizosphere colonization, etc. Efforts were devoted to produce the ?rst three volumes of the series on the biology of Pseudomonas after a meeting with Kluwer staff members in August 2002 during the XI IUMS conference in Paris (France). In less than a year a group of outstanding scientists in the ?eld, after devoting much of their valuable time, managed to complete their chapters for the three volumes of the series. To ensure the high standard of each chapter, renowned scientists participated in the reviewing process. The three books collected part of the "explosion" of new vital information on the genus Pseudomonas.

Cell-cell adhesion is fundamental for the development and homeostasis of animal tissues and organs. Adherens junctions (AJs) are the best understood cell-cell adhesion complexes. In this volume, a group of internationally recognized experts reviews AJ biology over a wide range of organization; from atoms to molecules, to protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development, pathogen infection and other diseases. This book addresses major questions encompassing AJ biology. * How did AJs evolve? * How do cadherins and catenins interact to assemble AJs and mediate adhesion? * How do AJs interface with other cellular machinery to couple adhesion with the whole cell? * How do AJs affect cell behaviour and multicellular development? * How can abnormal AJ activity lead to disease?

Plants have evolved with a complex array of signaling molecules to facilitate their growth and development and their interactions with the environment. A vast number of different peptide molecules form an important but until recently often overlooked component amongst these signaling molecules. Plant peptide signals are involved in regulating meristem growth and organogenesis, modulating plant growth and homeostatic responses. They also have important roles as signals of imminent danger or pathogen attack. This volume focuses on the roles of various peptide signaling molecules in development, defence and homeostasis. As it is likely that further plant peptide signaling molecules remain to be discovered, the last section takes a practical look at methods to identify new peptides and characterise their functions.

Methods in protein sequence analysis constitute important fields in rapid progress. We have experienced a continuous increase in analytical sensitivity coupled with decreases in time necessary for purification and analysis. Several generations of sequencers, liquid/solid/gas-phase, have passed by and returned in other shapes during just over two decades. Similarly, the introduction of HPLC permitted an enormous leap forward in this as in other fields of biochemistry, and we now start to see new major advances in purification/analysis through capillary electrophoresis. Furthermore, progress in the field of mass spectrometry has matched that in chemical analysis and we witness continuous development, now emphasizing ion spray and other mass spectrometric approaches. In short, protein analysis has progressed in line with other developments in modern science and constitutes an indispensable, integral part of present-day molecular biology. Even the available molecular tools, in the form of proteases with different specificities, have increased in number, although we still have far to go to reach an array of "restriction proteases" like the sets of nucleases available to the molecular geneticist. Of course, conferences have been devoted to protein sequence analysis, in particular the MPSA (Methods in Protein Sequence Analysis) series, of which the 8th conference took place in Kiruna, Sweden, July 1-6 1990. Again, we witnessed much progress, saw new instruments, and experienced further interpretational insights into protein mechanisms and functions.

The Symposium on "Protein Metabolism: Infiuence of Growth Hormone, Anabolie Steroids, and Nutrition in Health and Disease" is the fourth in the series of International Symposia sponsored by CIBA Limited, Basle. As in the case of the previous conferences, it was planned and organised with the help of experts in the field concerned. Special thanks are due to Prof. A. QuERIDO and Dr. A. A. H. KAssENAAR who, once the idea of the Symposium had been conceived in the course of joint discussions, embarked upon the project with enthusiasm and inspiration, although they must have known full weil what a great deal of time and trouble the organisation of such a meeting would inevitably cost them. For their untiring efforts, for the judicious manner in which they contrived to select precisely those subjects on which interest is chiefiy centred today, and-last but not least-for their success in finding competent specialists to participate in the proceedings, we wish to assure them of our sincere gratitude. To all the members of the Department of Clinical Endocrinology and Diseases of Metabolism, at the University Hospital in Leyden, who helped in preparing the meeting, we would likewise extend a warm vote of thanks. The fact that the present volume, featuring the papers and discussions of the Symposium, has been published only a few months after the event, was made possible thanks to the co operative help of all who participated.

In this brief, Vladimir Uversky discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). Beginning with an introduction to the concept of protein intrinsic disorder, Uversky then goes on to describe the peculiar amino acid sequences of IDPs, their structural heterogeneity, typical functions and disorder-based binding modes. In the final sections, Uversky discusses IDPs in human diseases and as potential drug targets. This volume provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.

Recent developments in computer science enable algorithms previously perceived as too time-consuming to now be efficiently used for applications in bioinformatics and life sciences. This work focuses on proteins and their structures, protein structure similarity searching at main representation levels and various techniques that can be used to accelerate similarity searches. Divided into four parts, the first part provides a formal model of 3D protein structures for functional genomics, comparative bioinformatics and molecular modeling. The second part focuses on the use of multithreading for efficient approximate searching on protein secondary structures. The third and fourth parts concentrate on finding 3D protein structure similarities with the support of GPUs and cloud computing. Parts three and four both describe the acceleration of different methods. The text will be of interest to researchers and software developers working in the field of structural bioinformatics and biomedical databases.

Michael D. Wendt Protein-Protein Interactions as Drug Targets Shaomeng Wang , Yujun Zhao , Denzil Bernard , Angelo Aguilar , Sanjeev Kumar Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics Kurt Deshayes , Jeremy Murray , Domagoj Vucic The Development of Small-Molecule IAP Antagonists for the Treatment of Cancer John F. Kadow , David R. Langley , Nicholas A. Meanwell , Michael A. Walker , Kap-Sun Yeung , Richard Pracitto Protein-Protein Interaction Targets to Inhibit HIV-1 Infection Nicholas A. Meanwell , David R. Langley Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion - a Focus on Respiratory Syncytial Virus Andrew B. Mahon , Stephen E. Miller , Stephen T. Joy , Paramjit S. Arora Rational Design Strategies for Developing Synthetic Inhibitors of Helical Protein Interfaces Michael D. Wendt The Discovery of Navitoclax, a Bcl-2 Family Inhibitor

The book contains chapters written by leaders in the research on the structure and function of respiratory complex I. It will provide a concise and authoritative summary of the current knowledge on complex I of respiratory chains. This enzyme is central to energy metabolism and is implicated in many human neurodegenerative diseases, as well as in aging. Until recently it was poorly understood on a structural level, and this book will provide a timely reference resource. Such a book was not published previously. The last time a minireview series on complex I were published was in 2001, and since then complex I field changed quite dramatically.

Cell surface molecules are critically important in regulating cell structure and function. Recent advances on the functional role of cell surface molecules, particularly glycoconjugates are presented in this book. Comprising of 22 chapters from the 2011 International Symposium on Biochemical Roles of Eukaryotic Cell Surface Macromolecules, it covers topics on the analysis of glycome, biophysical approaches to study cell surface molecules, glycoconjugate metabolism and its dysregulation, and molecular mechanisms involved in cell-cell and cell-matrix interaction.

The phrase "Life, stress and death" connects three terms, but is there a biological basis for that? Are there molecules that are essential to/or mediate these phenomena? This contributory volume "Mortalin Biology: Life, Stress and Death" is a remarkable compilation of the research outcomes on the stress protein mortalin, a member of heat shock 70 family of proteins. The book is unique as it describes mortalin playing essential role in life, stress response and death either from cancer, when it becomes hyperactive or from neuro-degeneration, when it becomes hypoactive. The book provides up-to-date knowledge on mortalin with respect to its discovery, structure, evolutionary conservation, function and signal transduction in different organisms in a simple, but most comprehensive way, that besides offering an enjoyable and in-depth reading, prompts the reader to ask further questions to explore this protein with new ideas, approaches and experiments. Twenty-one chapters by the world leaders on the specific areas of mortalin research throw light on its multi-functionality, potentials for biotechnology, diagnostics and therapeutic values. Avenues of mortalin biology, yet unexplored, hold immense promises for future, and reading this volume provides an easy, enthusiastic and energetic head-on start.

ABPP Methodology: Introduction and Overview, by Matthew B. Nodwell und Stephan A. Sieber Activity-Based Protein Profiling for Natural Product Target Discovery, by Joanna Krysiak und Rolf Breinbauer Photoaffinity Labeling in Activity-Based Protein Profiling, by Paul P. Geurink, Laurette M. Prely, Gijs A. van der Marel, Rainer Bischoff und Herman S. Overkleeft Application of Activity-Based Protein Profiling to the Study of Microbial Pathogenesis, by William P. Heal und Edward W. Tate Functional Analysis of Protein Targets by Metabolomic Approaches, by Yun-Gon Kim und Alan Saghatelian

This SpringerBrief explores the physiological roles of Skp1-Cullin1-F-box Complex (SCF) and Anaphase Promoting Complex (APC) in normal cells and in tumor formation. These two related, multi-subunit E3 ubiquitin ligase enzymes, APC and SCF are thought to be the major driving forces governing proper cell cycle progression. Defective cell cycle regulation leads to genomic instability and ultimately, cancer development. Selective degradation of key cell cycle regulators by the ubiquitin-proteasome system has been proven to be a major regulatory mechanism for ensuring ordered and coordinated cell cycle progression. The SCF and APC E3 ligases have been characterized to play pivotal roles in regulating the cell cycle progression by timely degrading various critical cell cycle regulators. This Brief reviews recent studies that have shown that deregulation of signaling pathways in which the two ubiquitin ligases are involved causes aberrant cell cycle regulation, in turn leading to tumorigenesis. The text also discusses how SCF and APC may present promising therapeutic targets to treat various cancers.

This book provides the basis for understanding the elastic properties of nucleic acids (DNA, RNA), the methods used to manipulate them (e.g. optical, magnetic and acoustic tweezers and traps), and how to observe their interactions with proteins (e.g. fluorescence microscopy, FCS, FRET, etc.). It then exemplifies the use of these various methods in the study of three families of DNA enzymes: polymerases, helicases and topoisomerases. The book aims not to be exhaustive, but rather to stimulate the imagination of readers in the application of these single molecule approaches to the study of DNA/RNA and their interactions.

Application of NMR and Molecular Docking in Structure-Based Drug Discovery, by Jaime L. Stark and Robert Powers NMR as a Unique Tool in Assessment and Complex Determination of Weak Protein-Protein Interactions, by Olga Vinogradova and Jun Qin The Use of Residual Dipolar Coupling in Studying Proteins by NMR, by Kang Chen und Nico Tjandra NMR Studies of Metalloproteins, by Hongyan Li and Hongzhe Sun Recent Developments in 15N NMR Relaxation Studies that Probe Protein Backbone Dynamics, by Rieko Ishima Contemporary Methods in Structure Determination of Membrane Proteins by Solution NMR, by Tabussom Qureshi and Natalie K. Goto Protein Structure Determination by Solid-State NMR, by Xin Zhao Dynamic Nuclear Polarization: New Methodology and Applications, by Kong Hung Sze, Qinglin Wu, Ho Sum Tse and Guang Zhu

Sequencing projects have revealed the presence of at least several hundred receptor kinases in a typical plant genome. Receptor kinases are therefore the largest family of primary signal transducers in plants, and their abundance suggests an immense signaling network that we have only just begun to uncover. Recent research findings indicate that individual receptor kinases fulfill important roles in growth and development, in the recognition of pathogens and symbionts or, in a few examples, in both growth and defense. This volume will focus on the roles of receptor kinases, their signaling pathways, and the ways in which these important signaling proteins are regulated.

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems."

This is a timely collection of important biomedical applications for a set of separation/characterization techniques that are rapidly gaining popularity due to their wide dynamic range, high resolution, and ability to function in most commonly used solvent systems. Importantly, the field-flow fractionation (FFF) technique has recently emerged as a prominent complement to size exclusion chromatography for protein pharmaceuticals. Fractionation with FFF is gentle and preserves protein structural integrity better than existing alternatives. In the present text, different chapters are written by experts in their respective field of application, who offer comparisons between the FFF techniques and other methods for characterizing their special focus material. Practical guide-lines for successful implementation, such as choice of operating conditions, are offered in conjunction with each application. In addition to new instrumentation and approaches that address important current topics, readers are provided with an overall sense of prior (but timeless) major developments that may be overlooked in literature searches.

In this volume we have brought together a number of core protocols concentrating on Protein, carefully written and edited by experts.
Indispensable tool for the researcher Carefully written and edited by experts to contain step-by-step protocolsIn this volume we have brought together a number of core protocols concentrating on Protein

This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.

"Laboratory Methods in Enzymology: Protein Part B" brings together a number of core protocols concentrating on protein, carefully written and edited by experts.
Indispensable tool for the researcher Carefully written and edited by experts to contain step-by-step protocolsIn this volume we have brought together a number of core protocols concentrating on protein

It can be concluded (under the specific experimental procedures em ployed) that: - 1) HCG labelled with 1 - 2 atoms of radioactive iodine did not differ sig nificantly from the unlabelled hormone; 2) The ovary alone exhibited a capacity to affix specifically HCG; 3) The amount of radioactive material in the ovary was directly proport ional to the quantity of labelled HCG injected; 4) When the HCG present in the circulation is bound to an antiserum to HCG, the antigen-antibody complex is not concentrated by the ovary; 5) Circulating labelled HCG decreased to 50% within 30 minutes following a single intravenous injection; 6) There are four different phases of ovarian uptake of HCG, namely: the first phase, when there is only an inflow from the circulation and stor age mainly in the follicular envelopes; the second phase, when there is a greater inflow than outflow; the third phase, when the inflow is equal to the outflow; and the fourth period, when the outflow is bigger than the in flow. REFERENCES 1. Lunenfeld, B. and Eshkol, A. Vitamins and Hormones (1967) 25:165 2. Eshkol, A. In: Recent Research on Gonadotropbio Hormones, eds. E. T. Bell andJ. A. Loraine, Edinburgh, Livingstone (1967), p. 202. 3. Eshkol, A. and Lunenfeld, B. Proc. Tel-Hashomer Hosp. (1967) 6:4. ACKNOWLEOOMEN'IS This work was supported in part by a grant from the Population Council, N. Y., U. S. A. andbyGrantNo."

Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers.