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Author: Kristian Henri Schlick Publisher: ISBN: Category : Carbohydrates Languages : en Pages : 380
Book Description
Understanding protein-carbohydrate interactions is essential for elucidating biological pathways and cellular mechanisms but is often difficult due to the prevalence of multivalent interactions. A better understanding of the basic behavior of protein-carbohydrate interactions is critical for controlling cellular proliferation and recognition processes for novel therapeutic methods to be successful. Many procedures that exist for evaluating protein-carbohydrate interactions are often limited to monovalent interactions or small polymers. Given that many cellular processes, such as those attributed to the immune system, are enhanced multivalently or are aggregation-driven, there is a need to reveal the behavior and basic requirements for multivalent binding and aggregation. Evaluating these interactions on large, multivalent scaffolds such as synthetically controllable dendrimers provides an important tool towards accurately determining the role of glycosylation in biological systems. Here, different approaches to measure the interactions of proteins with glycodendrimers are described, ranging from simple qualitative assays to novel quantitative methods of assessment. Quantitative methods such as Isothermal Titration Calorimetry and Surface Plasmon Resonance are severely limited when used with multivalent systems, and do not provide as accurate results as monovalent systems. When dealing with multivalent systems, inhibition assays often provide more reproducible results. Through these experiments, it has become increasingly apparent that aggregates play a significant role in multivalent systems, and current methods to evaluate these interactions leave much room for improvement. Assay design is important both for basic identification and understanding of any interaction, especially higher-order interactions involving multivalency. Endgroup patterning and presentation was explored to determine their role in multivalent affinity enhancements. Using a novel fluorescence lifetime method, glycodendrimer-mediated aggregation was successfully characterized. The work here evaluates the effectiveness of assays used for carbohydrate interaction, translated to a multivalent scaffold, with special consideration to large-order aggregates.
Author: Kristian Henri Schlick Publisher: ISBN: Category : Carbohydrates Languages : en Pages : 380
Book Description
Understanding protein-carbohydrate interactions is essential for elucidating biological pathways and cellular mechanisms but is often difficult due to the prevalence of multivalent interactions. A better understanding of the basic behavior of protein-carbohydrate interactions is critical for controlling cellular proliferation and recognition processes for novel therapeutic methods to be successful. Many procedures that exist for evaluating protein-carbohydrate interactions are often limited to monovalent interactions or small polymers. Given that many cellular processes, such as those attributed to the immune system, are enhanced multivalently or are aggregation-driven, there is a need to reveal the behavior and basic requirements for multivalent binding and aggregation. Evaluating these interactions on large, multivalent scaffolds such as synthetically controllable dendrimers provides an important tool towards accurately determining the role of glycosylation in biological systems. Here, different approaches to measure the interactions of proteins with glycodendrimers are described, ranging from simple qualitative assays to novel quantitative methods of assessment. Quantitative methods such as Isothermal Titration Calorimetry and Surface Plasmon Resonance are severely limited when used with multivalent systems, and do not provide as accurate results as monovalent systems. When dealing with multivalent systems, inhibition assays often provide more reproducible results. Through these experiments, it has become increasingly apparent that aggregates play a significant role in multivalent systems, and current methods to evaluate these interactions leave much room for improvement. Assay design is important both for basic identification and understanding of any interaction, especially higher-order interactions involving multivalency. Endgroup patterning and presentation was explored to determine their role in multivalent affinity enhancements. Using a novel fluorescence lifetime method, glycodendrimer-mediated aggregation was successfully characterized. The work here evaluates the effectiveness of assays used for carbohydrate interaction, translated to a multivalent scaffold, with special consideration to large-order aggregates.
Author: Diana Zanini Publisher: ISBN: Category : Languages : en Pages : 0
Book Description
The syntheses and {\it in vitro\/} biological evaluation of three series of glycodendrimers is presented herein. This dissertation marks three ``firsts'' in the field of glycobiology. Chemically well defined hypervalent neoglycoconjugates, termed glycodendrimers, have been designed and prepared. These concepts were extended to include the enzymatic elongation of a glycoside on a dendritic core. Furthermore, the first direct correlation of the number of carbohydrate residues and the multivalent effect has been reported. To further the understanding of multivalency and its role in carbohydrate-protein interactions, glycoconjugates with differing carbohydrate densities, conformations, and interglycosidic spacings must be prepared. The design and synthesis of glycodendrimers addresses these issues. Solid phase synthesis on Wang resin was used to construct dendritic $\alpha$-thiosialosides. The design of these new, hyperbranched clusters was based on the rational scaffolding of L-lysine core structures using established 9-fluorenylmethoxycarbonyl (Fmoc) protecting group and activated benzotriazolyl ester (HOBt) coupling procedures. Chain extension of the lysyl amino groups with chloroacetylglycylglycine active ester allowed introduction of the required functionality necessary for the coupling to an $\alpha$-thiosialoside derivative prepared under phase transfer catalysed conditions. Well defined di-, tetra-, octa-, and hexadeca-valent dendritic $\alpha$-thiosialosides were thus prepared. The synthesis of structurally similar divergent and spherical dendrimers, with even valencies of between two and sixteen and ending with equidistant $\alpha$-thiosialoside residues is also described. The synthesis of the dendritic core was based on the regioselective protection of the primary amines of 3,3$\sp\prime$-iminobis(propylamine) using benzylcyanoformate. The resulting secondary amine was monoalkylated with {\it tert\/}-butyl bromoacetate to provide a divalent core structure orthogonally protected with carbobenzyloxy (Cbz) protected amines and a {\it tert\/}-butyl ester. Selective deprotection {\it via\/} hydrogenation or trifluoroacetolysis afforded amine and acid key precursors, respectively. These were conjugated using standard HOBt/DIC strategy to give divergent, Cbz-protected dendrimers with valencies between two and sixteen in the first through fourth generations. Tethering of the dimer and tetramer to both hexamethylenediamine and tris-(2-aminoethyl)amine provided spherical, hyperbranched dendritic structures with valencies between four and twelve. All Cbz-protected dendrimers were transformed into N-chloroacetylated dendrimers which were coupled to a thiolated sialic acid derivative. Thiourelene {\it p\/}-phenyl $\alpha$-thiosialoside containing dendrimers scaffolded on Starburst$\sp\circler$ PAMAM dendrimers were prepared using an isothiocyanate conjugation strategy. PAMAM cores, generation G0 to G3, were coupled to a sialic acid isothiocyanate derivative to give spherical, hypervalent thiourea derivatives containing four to thirty-two surface sialic acid residues. The above concepts were easily extended to include the preparation of dendrimers with covalently attached N-acetylglucosamine, lactose, N-acetyllactosamine, mannose, Gal$\beta$-(1,3)-GalNAc$\alpha$ (T-antigen), and 3$\sp\prime$-sulfo-Lewis$\sp{\rm X}$-(Glc) residues. Furthermore, glycodendrimers were shown to be amenable to both chemical and enzymatic transformations {\it via\/} the 9-O-acetylation of octavalent $\alpha$-thiosialodendrimers and the enzymatic galactosylation of dendritic N-acetylglucosamine. The preparation of a custom designed heterobifunctional dendrimer containing biotin and four sialic acid residues is also presented. The synthesis was based on the tethering of a tetravalent, Cbz-protected, 3,3$\sp\prime$-iminobis(propylamine)-based core to an amine functionalized biotin derivative using established HOBt/DIC coupling chemistry. Cbz deprotection {\it via\/} hydrogenation afforded the biotin-containing tetraamine which was conjugated to a sialic acid {\it p\/}-isothiocyanatophenyl derivative to provide the desired bi-directional glycodendrimer. Binding studies {\it via\/} double immunodiffusion and/or turbidimetric analysis confirmed the ability of the glycodendrimers to cross-link and precipitate appropriate model lectins. In addition, when used in competitive enzyme linked lectin assays, all glycodendrimers showed improved inhibitory potentials.
Author: Bertram O. Fraser-Reid Publisher: Springer Science & Business Media ISBN: 3540361545 Category : Science Languages : en Pages : 2847
Book Description
As a reflection of the quantum leap that has been made in the study of glycostructures, the first edition of this book has been completely revised and updated. The editors give up-to-date information on glycostructures, their chemistry and chemical biology in the form of a completely comprehensive survey. Glycostructures play highly diverse and crucial roles in a myriad of organisms and important systems in biology, physiology, medicine, bioengineering and technology. Only in recent years have the tools been developed to partly understand the highly complex functions and the chemistry behind them. While many facts remain undiscovered, this MRW has been contributed to by a large number of the world’s leading researchers in the field.
Author: Ravin Narain Publisher: John Wiley & Sons ISBN: 1118002245 Category : Technology & Engineering Languages : en Pages : 416
Book Description
This book addresses the need for a comprehensive book on the design, synthesis, and characterization of synthetic carbohydrate-based polymeric materials along with their biological applications. The first two chapters cover the synthesis and self-assembly of glycopolymers and different techniques for creating these synthetic polymers. Subsequent chapters account for the preparation of block copolymers, branched glycopolymers, glycosurfaces, glycodendrimers, cationic glycopolymers, bioconjugates, glyconanoparticles and hydrogels. While these chapters comprehensively review the synthetic and characterization methods of those carbohydrate-based materials, their biological applications are discussed in detail.
Author: Binghe Wang Publisher: John Wiley & Sons ISBN: 0470592079 Category : Medical Languages : en Pages : 448
Book Description
This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.
Author: Jurriaan Huskens Publisher: John Wiley & Sons ISBN: 1119143462 Category : Science Languages : en Pages : 434
Book Description
Connects fundamental knowledge of multivalent interactions with current practice and state-of-the-art applications Multivalency is a widespread phenomenon, with applications spanning supramolecular chemistry, materials chemistry, pharmaceutical chemistry and biochemistry. This advanced textbook provides students and junior scientists with an excellent introduction to the fundamentals of multivalent interactions, whilst expanding the knowledge of experienced researchers in the field. Multivalency: Concepts, Research & Applications is divided into three parts. Part one provides background knowledge on various aspects of multivalency and cooperativity and presents practical methods for their study. Fundamental aspects such as thermodynamics, kinetics and the principle of effective molarity are described, and characterisation methods, experimental methodologies and data treatment methods are also discussed. Parts two and three provide an overview of current systems in which multivalency plays an important role in chemistry and biology, with a focus on the design rules, underlying chemistry and the fundamental principles of multivalency. The systems covered range from chemical/materials-based ones such as dendrimers and sensors, to biological systems including cell recognition and protein binding. Examples and case studies from biochemistry/bioorganic chemistry as well as synthetic systems feature throughout the book. Introduces students and young scientists to the field of multivalent interactions and assists experienced researchers utilising the methodologies in their work Features examples and case studies from biochemistry/bioorganic chemistry, as well as synthetic systems throughout the book Edited by leading experts in the field with contributions from established scientists Multivalency: Concepts, Research & Applications is recommended for graduate students and junior scientists in supramolecular chemistry and related fields, looking for an introduction to multivalent interactions. It is also highly useful to experienced academics and scientists in industry working on research relating to multivalent and cooperative systems in supramolecular chemistry, organic chemistry, pharmaceutical chemistry, chemical biology, biochemistry, materials science and nanotechnology.
Author: Publisher: Academic Press ISBN: 0123808553 Category : Science Languages : en Pages : 562
Book Description
Since its inception in 1945, this serial has provided critical and integrating articles written by research specialists that integrate industrial, analytical, and technological aspects of biochemistry, organic chemistry, and instrumentation methodology in the study of carbohydrates. The articles provide a definitive interpretation of the current status and future trends in carbohydrate chemistry and biochemistry. - Features contributions from leading authorities and industry experts - Informs and updates on all the latest developments in the field
Author: Yann Chevolot Publisher: Humana Press ISBN: 9781617793721 Category : Science Languages : en Pages : 427
Book Description
Carbohydrate microarrays emerged as a key technology for the deciphering of the glycospace by providing a multiplex technology where tens to hundreds of carbohydrates/protein interactions can be probed in parallel. Carbohydrate Microarrays: Methods and Protocols aims to give the reader the theoretical and experimental clues necessary for the fabrication and implementation of carbohydrate microarrays. This requires three essential steps: 1) to obtain the carbohydrate probes (monosacharides, oligosacchrides, polysacchairdes, glycoconjugates or glycoclusters), 2) to immobilize these probes, and 3) to implement the protocols for biological/biochemical interaction with the desired target. This volume gives an overview of carbohydrate microarray and carbohydrate chemistry and illustrates different detection techniques and their applications. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Carbohydrate Microarrays: Methods and Protocols compiles a catalogue of protocols on carbohydrate microarrays to span the needs of researchers around the globe.
Author: Kristian Henri Schlick
Author: Kristian Henri Schlick
Author: Diana Zanini
Author: Ioannis Vrasidas
Author: Bertram O. Fraser-Reid
Author: Ravin Narain
Author: Binghe Wang
Author: Jurriaan Huskens
Author: 
Author: Yee Chun Lee
Author: Yann Chevolot