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Iminosugars form undoubtedly the most attractive of carbohydrate mimics reported so far. In these structures, the substitution of the endocyclic oxygen of sugars by a basic nitrogen atom leads to remarkable biological properties and raises many challenges in organic synthesis. Since the discovery of their biological activity as glycosidase inhibitors in the 1970’s, these polyvalent molecules have progressively made their way from the laboratory to the clinic. The impressive series of discoveries in the field over the past ten years indicates clearly that it is “a boom time” for iminosugar chemistry and biology. The scope of their profile as inhibitors has been extended to a number of enzymes such as phosphorylases, glycosyltransferases or metalloproteinases, and iminosugars now constitute lead compounds for the development of new therapeutic agents for a wide range of diseases including diabetes, viral infections, lysosomal storage disorders and tumor metastasis. Latest developments, from iminosugar synthesis to their use in clinical studies, are presented in this book, which contains contributions from over fifteen of the major chemists, biochemists and drug developers in this rapidly expanding field. An extensive table correlating the structures of more than 600 iminosugars of therapeutic interest with their biological activities is also included in the book and should prove particularly useful to aid with the design and the discovery of novel bioactive substances. Iminosugars: From Synthesis to Therapeutic Application provides a unique resource for academic and industrial researchers working in the field of iminosugars and glycomimetics of biological and/or therapeutic interest: organic chemists, medicinal chemists, carbohydrate chemists and medical scientists.
Carbohydrate Chemistry demonstrates the interdisciplinary nature of modern carbohydrate research, and benefits any researcher who wishes to learn about the latest developments in the carbohydrate field.
This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.
This book contains the best known approaches for preparing the main types of glycosides in a short and comprehensive study. It also includes synthetic pathways of challenging glycosides known as antiviral or antineoplasic drugs, or synthetic substrates used for enzymatic detection including those used as substrates for detection of gene markers in plant biotechnology. Special attention is made on the structural characterization, providing the basic tools for the structural assignment through NMR, X-Ray and mass spectra techniques. Some of the chapters cover strategies for preparation of antiviral and antineoplasic drugs included in a drug design course.
Protein Homeostasis Diseases: Mechanisms and Novel Therapies offers an interdisciplinary examination of the fundamental aspects, biochemistry and molecular biology of protein homeostasis disease, including the use of natural and pharmacological small molecules to treat common and rare protein homeostasis disorders. Contributions from international experts discuss the biochemical and genetic components of protein homeostasis disorders, the mechanisms by which genetic variants may cause loss-of-function and gain-of-toxic-function, and how natural ligands can restore protein function and homeostasis in genetic diseases. Applied chapters provide guidance on employing high throughput sequencing and screening methodologies to develop pharmacological chaperones and repurpose approved drugs to treat protein homeostasis disorders. - Provides an interdisciplinary examination of protein homeostasis disorders, with an emphasis on treatment strategies employing small natural and pharmacological ligands - Offers applied approaches in employing high throughput sequencing and screening to develop pharmacological chaperones to treat protein homeostasis disease - Gathers expertise from a range of international chapter authors who work across various biological methods and disease specific disciplines of relevance
In this volume, glycochemistry and glycobiology have been combined to demonstrate the contribution of organic chemistry, modern analytics, biological and biochemical expertise to the increasingly important field of glycomics. A polysaccharide immunomodulator with therapeutic implications, carbohydrate vaccines, new findings emphasizing the influence of carbohydrate decoration on the regulation of inflammatory response and new therapeutic approaches in the treatment of acute and chronic inflammatory diseases, recent progress on glycoengineering based on a glycosylation strategy to optimize protein drugs, congenital disorders of glycosylation, and key aspects of the glycosylation changes associated with bladder cancer are amongst the subjects presented in this volume. The contribution of glycochemistry to innovation in glycosciences is shown with chapters covering highly functionalized exo-glycals for the generation of molecular diversity in a chemoselective manner, imino sugar glycosidase inhibitors, carbasugars, multivalent glycoconjugates, including glycodendrimers, glyconanotubes, and glyconanoparticles, and their uses in medicinal chemistry, as well as artificial saccharide-based and saccharide-functionalized gene delivery systems. Siderophores based on monosaccharides (which have proven effective for Gram-negative bacteria and mycobacteria), and the so-called smart materials, (which can modulate and control cell behaviour), complete the volume. Volume 39 of Carbohydrate Chemistry - Chemical and Biological Approaches contains contributions ranging from glycochemistry to glycobiology. This collection demonstrates in a meaningful way how the interdisciplinary approach of an international glyconetwork can advance the field of carbohydrate research in Europe and worldwide.
The so-called postgenomic research era has now been launched, and the field of gly cobiology and glycotechnology has become one of the most important areas in life science because glycosylation is the most common post-translational modification reaction of proteins in vivo. On the basis of Swiss-Prot data, over 50% proteins are known to undergo glycosylation, but in fact the actual functions of most of the sugar chains in the glycoconjugates remain unknown. The complex carbohydrate chains of glycoproteins, glycolipids, and proteoglycans represent the secondary gene products formed through the reactions of glycosyl transferases. The regulation of the biosynthesis of sugar chains is under the control of the expression of glycosyltransferases, their substrate specificity, and their local ization in specific tissue sites. There is a growing body of evidence to suggest that these enzymes play pivotal roles in a variety of important cellular differentiation and developmental events, as well as in disease processes. Over 300 glycosyltransferases appear to exist in mammalian tissues. If the genes that have been purified and cloned from various species such as humans, cattle, pigs, rats and mice are counted as one, approximately 110 glycogenes that encode glycosyltransferases and related genes have been cloned at present, and this number continues to grow each day. However, most of the functions of the glycosyltransferase genes and related genes are unknown. This fact has stimulated numerous new and interesting approaches in molecular biologi cal investigations.
This series presents critical reviews of the present position and future trends in modern chemical research. The short and concise reports on chemistry, each written by the world’s renowned experts, are still valid and useful after 5 or 10 years.
This contributed volume contains 25 chapters from leading international scientists working on dengue and Zika viruses, who came together in Praia do Tofo in Mozambique to discuss the latest developments in the fields of epidemiology, pathogenesis, structural virology, immunology, antiviral drug discovery and development, vaccine efficacy, and mosquito control programs. The meeting venue offered an opportunity to discuss current research on these flaviviruses in an idyllic setting, and also to develop first-hand appreciation of the issues in infectious diseases facing developing countries and of the research gaps in Africa. For readers, who should include basic and clinical researchers in the field and public health professionals, the chapters are organized to provide a comprehensive overview of the various topics in current dengue and Zika virus research. A unique feature of the proceedings of this meeting is the inclusion of the discussions that took place following presentations. These have been transcribed and appended to the end of the relevant chapters, and they form the “salt in the soup” of this book.
This book contains original papers and reviews on carbohydrate research in medicine, authored by participants of the 29th International Carbohydrate Symposium, where this topic had a special emphasis. The focus on biological events involving carbohydrates and glycoconjugates has delivered reliable approaches for disease treatment and diagnosis. Research on carbohydrate-based compounds for therapeutic applications is illustrated in various contributions, namely those covering the development of novel agents against Alzheimer’s disease, e.g. the neuroprotective C-glucosylated flavones and the isonucleoside-based cholinesterase inhibitors. New imino sugar glucosidase inhibitors are also disclosed, a class of compounds with potential for diabetes, Gaucher disease or cancer treatment. Also the development of a useful synthetic method towards multivalent glycoclusters of biomedical interest is here highlighted. The relevance of glycomimetics in drug discovery and the progress on carbohydrates in early diagnosis and cancer treatment are reviewed. Noteworthy is the chitosan-based delivery system for drug oral administration, a new biomaterial-based approach to improve bioavailability. Another study on the conformation of Streptococcus capsular polysaccharide backbones by molecular modelling provides useful information for bacterial immunotherapeutic approaches. All original contributions and reviews clearly demonstrate the potential of glycosciences for innovation in medicinal (glyco)chemistry and pharmaceutical research.