[PDF] Synthesis Of Glycoproteins And C Linked Glycopeptides eBook

Author : Valentin Wittmann
Publisher : Springer Science & Business Media
Page : 271 pages
File Size : 28,37 MB
Release : 2007-02-13
Category : Science
ISBN : 3540367608

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In the last 50 years molecular biology was dominated by the exploration of proteins and nucleic acids. Beside their role in energy metabolism, oligos- charides,which represent thethirdclass ofbiomacromolecules, have received less attention. Today it is well established that oligosaccharides are involved in many important biologicalregulation and recognition processes fromp- tein folding to cell-cell communication. Glycosylation of proteins is the most complexformofco-andposttranslationalmodi'cation. Thedeterminationof structure-function relationships, however, remains dif'cult due to the mic- heterogeneity of glycoproteins that exist in many different glycoforms. Thus chemical synthesis of glycoproteins and glycopeptides with de'ned glycan structures plays a pivotal role for the detailed determination of the role of protein glycosylation. This topic is covered by the ?rst two chapters of this bookdealingwiththechemicaland enzymatic synthesis ofglycopeptides and glycoproteins. The third chapter describes the construction of glycopeptide andglycoproteinmimetics containingnon-naturalstructuralelements. These so-calledneoglycopeptidesandneoglycoproteins,respectively,canprovide- sight on the importance of distinct structural elements on biological activity andmayhaveimproved propertiessuchasanincreased stability. Theappli- tion of synthetic glycopeptides, in many cases at the clinical level, as vaccines forbothcancerandHIVisthesubjectofthefourthchapter. Glycopeptide antibiotics are glycosylated secondary metabolites of bacteria and fungi that are synthesized by non-ribosomal peptide synthetases. Some of them serve as antibiotics of last resort in the treatment of nosocomial infections with enterococci and methicillin-resistant Staphylococcus aureus (MRSA) strains. Their structure, biosynthesis, and mode of action are summarized in the ?fth chapter. The last chapter covers current methods for the determination of high-resolution structures of glycopeptides and glycoproteins mainly based onNMRspectroscopy, X-raycrystallography,and molecular modeling.

Author : David G. Large
Publisher : CRC Press
Page : 786 pages
File Size : 36,96 MB
Release : 1997-05-06
Category : Medical
ISBN : 9780824795313

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"Presents state-of-the-art methods for the synthesis, analysis, and conformational investigation of glycoproteins and glycopeptides. Discusses the history of glycopeptide synthesis, therapeutic applications, and the future of research."

Author : Zhongping Tan
Publisher : Royal Society of Chemistry
Page : 441 pages
File Size : 29,2 MB
Release : 2017-03-27
Category : Science
ISBN : 1782623337

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Glycans play a vital role in modulating protein structure and function from involvement in protein folding, solubility and stability to regulation of tissue distribution, recognition specificity, and biological activity. They can act as both positive and negative regulators of protein function, providing an additional level of control with respect to genetic and environmental conditions. Due to the complexity of glycosylated protein forms, elucidating structural and functional information has been challenging task for researchers but recent development of chemical biology-based tools and techniques is bridging these knowledge gaps. This book provides a thorough review of the current state of glycoprotein chemical biology, describing the development and application of glycoprotein and glycan synthesis technologies for understanding and manipulating protein glycosylation.

Author : CI Xu
Publisher : Open Dissertation Press
Page : pages
File Size : 16,83 MB
Release : 2017-01-27
Category :
ISBN : 9781361381427

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This dissertation, "Towards synthesis of glycopeptides/glycoproteins via serine/threonine ligation" by Ci, Xu, 许辞, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Glycoproteins are proteins that are post-translationally modified with oligosaccharides. Due to the non-template-mediated biosynthesis of glycoproteins in the nature, glycoproteins always exist as heterogeneous mixtures with different glycan structures. In order to obtain the homogeneous glycoproteins with the well-defined glycan structures for an extensive investigation of the relationship between the structure and function of glycoproteins, synthetic strategies including chemical and chemoenzymatic synthesis have been employed and achieved great success over the past years. Among these approaches, our research group has developed a novel serine/threonine ligation (STL), which involved a chemoselective ligation between a peptide with a salicylaldehyde (SAL) ester at the C-terminus and an N-terminal serine or threonine of another peptide to generate the natural Xxx-Ser/Thr linkage (Xxx represents any amino acid) at the conjugation site. STL provides more possibilities for disconnection sites for convergent protein/glycoprotein synthesis. My research has been focused on the synthesis of MUC1 glycopeptides. MUC1 is a transmemberane glycoprotein expressed on the apical surface of most normal epithelial cells at low levels but highly overexpressed on the entire membrane of human epithelial tumor cells. In the extracellular part, MUC1 contains a variable number of tandem repeat (VNTR) units which consist of twenty amino acids with five potential O-glycosylation sites. As MUC1 has been shown asa promising target for the production of immunostimulating antigens, a variety of chemical assembly strategies have been applied for the development of MUC1 glycopeptide-based anticancer vaccines with high immunogenicity and tumor selectivity, including the construction of multivalent dendrimers presenting tumor-associated MUC1 glycopeptide antigens and the incorporation of various immunoadjuvants. In my studies, I have successfully synthesized the large MUC1 VNTR glycopeptides (40-mer and 80-mer sections) possessing tumor-associated Tn antigens via one and three consecutive STL reactions. On the other hand, the cyclic MUC1 glycopeptide-BSA conjugates has been successfully constructed. We are yet to test the immunological properties of synthetic MUC1 glycopeptide oligomers and MUC1-based glycoconjugates as anticancer vaccine candidates. In addition, inspired by STL, I have developed an aspartic acid ligation, in which a C-terminal peptide-SAL ester chemoselectively reacts with an N-terminal diol group of another peptide under the same conditions as STL to form a six-membered N, O-benzylidene acetal linked intermediate. Followed by treatment with acidsand selectiveoxidation, the natural Xxx-Asplinkage(Xxx represents any amino acid) is chemoselectively generated at the conjugation site. This STL-based aspartic acid ligation has been applied in the synthesis of a series of cyclic and linear peptides. Subjects: Glycopeptides - Synthesis Glycoproteins - Synthesis

Author : Yu-Ying Yang
Publisher :
Page : 400 pages
File Size : 37,12 MB
Release : 2007
Category : Glycopeptides
ISBN : 9780549110033

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Based on the same principle of native chemical ligation and auxiliary-assisted ligation, we recently developed the "sugar-assisted ligation" method for glycopeptide and glycoprotein synthesis. In this method, we take the advantage of sugar by anchoring a thiol handle onto the C2 position of sugar moiety to facilitate the transthioesterification followed by S to N acyl transfer. The sugar moiety utilizes its rigid conformation to bring the two reacting groups of thioester intermediate into close proximity to facilitate acyl transfer. The ligation junction in sugar-assisted ligation tolerates a broad spectrum of amino acids with high preference to less hindered residues (Gly, Ala) and those with side chain that can serve as a general base (His, Asp) in the ligation pathway. The utility of this ligation method has been demonstrated in the successful synthesis of [beta]-O-linked glycopeptides, N-linked glycopeptides, [alpha]-O-linked glycopeptide and "mucin-type" [alpha]-O-linked glycoproteins. Enzymatic peptide ligation using subtilisin BPN' 8397 was also exploited here for the synthesis of a-linked glycopeptides. Under the kinetically-controlled conditions, we successfully performed the enzymatic ligations where N-linked, [alpha]-O-linked or [alpha]-S-linked glycopeptides reacted as the acyl donors. In comparison with N-linked glycopeptides, [alpha]-linked glycopeptide, where the sugar moieties located at their P2 positions, showed superior enzymatic ligation efficiencies. On the other hand, to further explore the utility of expressed protein ligation method on the synthesis of glycosylated hIL-2, we continued our previous efforts here to synthesize the native hIL-2 glycoform. We utilized the highly-specific TEV protease to remove the affinity tag from recombinant His-tagged hIL-2, and unmasked the N-terminal cysteine for ligation. Various glycopeptide thioesters, which were synthesized by chemical or chemo-enzymatic methods, were ligated to truncated IL-2 fragment (residues 6-133). The ligation studies suggested that moving the sugar moiety farther away from the ligation junction is able to improve the ligation yield. Besides, in order to isolate the ligation product from other protein mixtures, we developed and tested several affinity chromatography methods to purify glycosylated human IL-2.

Author : Tamao Endo
Publisher : Springer
Page : pages
File Size : 50,78 MB
Release : 2021-01-14
Category : Science
ISBN : 9784431548362

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The aim of the book is to provide a succinct overview of the current status of glycoscience from both basic biological and medical points of view and to propose future directions, in order to facilitate further integrations of glycoscience with other fields in biological and medical studies. Glycans (carbohydrate oligomers) are the so-called “building blocks” of carbohydrates, nucleic acids, proteins and lipids and play major roles in many biological phenomena as well as in various pathophysiological processes. However, this area of glycoscience has been neglected from the research community because glycan structures are very complex and functionally diverse and as compared to proteins and nucleic acids simple tools for the amplification, sequencing and auto-synthesis of glycans are not available. Many scientists in other fields of research have now realized that glycosylation, i.e. the addition of glycans to a protein backbone, is the most abundant post translational modification reactions and is an important field of research and sometimes they require a glycobiology and/or glycochemistry approach to be used. It is still difficult, however, for non-expert researchers to use these techniques. This book will provide numerous but simple overviews of current topics and protocols for the experiments. The book is aimed at university students and above, including non-experts in the field of glycoscience.

Author : N Saraswathy
Publisher : Elsevier
Page : 271 pages
File Size : 23,82 MB
Release : 2011-07-01
Category : Science
ISBN : 1908818050

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Concepts and techniques in genomics and proteomics covers the important concepts of high-throughput modern techniques used in the genomics and proteomics field. Each technique is explained with its underlying concepts, and simple line diagrams and flow charts are included to aid understanding and memory. A summary of key points precedes each chapter within the book, followed by detailed description in the subsections. Each subsection concludes with suggested relevant original references. Provides definitions for key concepts Case studies are included to illustrate ideas Important points to remember are noted

Author : Luca D. D'Andrea
Publisher : John Wiley & Sons
Page : 492 pages
File Size : 49,89 MB
Release : 2017-04-03
Category : Science
ISBN : 1119044103

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Presenting a wide array of information on chemical ligation – one of the more powerful tools for protein and peptide synthesis – this book helps readers understand key methodologies and applications that protein therapeutic synthesis, drug discovery, and molecular imaging. • Moves from fundamental to applied aspects, so that novice readers can follow the entire book and apply these reactions in the lab • Presents a wide array of information on chemical ligation reactions, otherwise scattered across the literature, into one source • Features comprehensive and multidisciplinary coverage that goes from basics to advanced topics • Helps researchers choose the right chemical ligation technique for their needs