Comprehensive Natural Products II: Chemistry and Biology: Carbohydrates, Nucleosides & Nucleic Acids Volume 6

Annotation. This work presents a definitive interpretation of the current status of and future trends in natural products-a dynamic field at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids, and enzymes. With more than 1,800 color figures, Comprehensive Natural Products II features 100% new material and complements rather than replaces the original work (©1999). * Reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine * Stimulates new ideas among the established natural products research community-which includes chemists, biochemists, biologists, botanists, and pharmacologists * Informs and inspires students and newcomers to the field with accessible content in a range of delivery formats 1 CONAP_Contents_all_volumes......Page 1 Overview......Page 13 Introduction......Page 16 Glycosidases in Carbohydrate Synthesis......Page 19 Conclusion......Page 25 Mechanisms of Glycosynthases......Page 26 Glycosynthases in Carbohydrate Synthesis......Page 28 Conclusion......Page 33 Sugar Nucleotide Biosynthetic Pathway......Page 34 Enzyme-based complex saccharide synthesis......Page 36 Conclusion......Page 57 Outlook......Page 58 Abbreviations......Page 59 References......Page 60 Introduction......Page 66 Nature of Glycopeptide and Glycoprotein......Page 67 Neoglycopeptide......Page 68 Synthesis of Glycopeptides......Page 69 Solution-Phase Synthesis......Page 70 Solid-Phase Synthesis......Page 72 Enzymatic Synthesis......Page 77 Chemical Ligation......Page 80 C-Linked Glycopeptides......Page 86 Oxime-Linked Glycopeptides......Page 88 S-Linked Glycopeptides......Page 89 Glycoprotein Synthesis......Page 90 Chemical Approaches......Page 91 Biochemical Approaches......Page 94 Abbreviations......Page 95 References......Page 96 Introduction......Page 101 TACA Expression......Page 102 Mechanism of TACA Expression......Page 103 Immunogenicity of Carbohydrates and Immunotolerance to TACAs......Page 104 In vitro enzymatic synthesis of TACAs and TACA conjugates......Page 105 In vivo metabolic engineering to obtain TACAs and TACA conjugates......Page 106 Immunological Adjuvant Application......Page 107 Semisynthetic Glycoconjugate Cancer Vaccines......Page 108 Semisynthetic monovalent glycoconjugate vaccines......Page 109 Semisynthetic monovalent clustered glycoconjugate vaccines......Page 112 Semisynthetic multivalent glycoconjugate vaccines......Page 115 Two-component fully synthetic glycoconjugate vaccines......Page 117 Three-component fully synthetic glycoconjugate vaccines......Page 120 Four-component fully synthetic glycoconjugate vaccines......Page 122 Cancer vaccines made of chemically modified sialo-TACAs......Page 123 Cancer immunotherapy based on modified sialo-TACAs vaccines and cancer cell glycoengineering......Page 124 Conclusion......Page 125 References......Page 126 MS-Based Glycoanalysis......Page 133 Introduction......Page 134 Factors determining the glycosylation structures - how much can be assumed a priori?......Page 135 Structural Architecture and Diversity......Page 136 The common core structures......Page 137 Workflows in MS-Based Protein Glycosylation Analysis......Page 138 Defining the Conceptual Framework......Page 139 From biological source to solubilized glycoproteins......Page 140 Glycan release and reducing end tagging......Page 141 Permethylation and other related chemical derivatization......Page 142 Glycan fractionation and targeted enrichment......Page 143 Glycopeptide enrichment......Page 144 MALDI versus ESI-MS and MS/MS......Page 145 Qualitative versus quantitative MS mapping......Page 147 Glycosidic Cleavages and Oxonium Ions......Page 149 Neutral loss and identification of core structures......Page 150 Nonreducing terminal oxonium and B ions......Page 151 Cross-Ring and Other Linkage-Specific Cleavages......Page 152 Negative ion mode sequencing of native glycans......Page 153 MSn of permethylated glycans......Page 155 High-energy CID-MS/MS on MALDI-TOF/TOF of permethylated glycans......Page 156 Resolving the Glycomic Complexity by MS/MS......Page 157 Glycosylation and glycomic mapping at MS2 level......Page 158 Prospects for Targeted Glycomics......Page 159 Current limitations in glycopeptide analysis......Page 160 Concluding Remarks......Page 161 References......Page 162 Introduction......Page 167 N-Glycosylation......Page 168 Lipopolysaccharide......Page 169 Analysis of O-deacylated LPS......Page 170 Core analysis......Page 173 Lipid A analysis......Page 174 S-Type LPS......Page 175 Capsular Polysaccharides......Page 178 Abbreviations......Page 179 References......Page 180 Introduction......Page 184 Role of Glycan Epitopes in Mediating Cell-Cell Interactions......Page 185 Glycosaminoglycans......Page 186 Glycolipids/Gangliosides......Page 190 Carbohydrate Roles in Bacteria and Mycobacteria......Page 192 Chemoenzymatic Synthesis to Study Glycan Structure and Function......Page 196 Alternative Nucleotide Sugar Donors......Page 198 Chemoenzymatic Synthesis of Sialic Acids......Page 202 Metabolic Flux of Unnatural Sugar Analogs and Effects on Cell Viability......Page 206 Polysialic Acid Function......Page 209 Metabolically Engineered Gangliosides for Cancer Immunotherapy......Page 211 Covalently Trapping Glycan Interactions with Photocross-linkers......Page 213 Sugar Probes for Lectin Characterization and Discovery......Page 214 Cross-linking Glycolipids......Page 219 Metabolic Incorporation of Cross-linking Sugars......Page 223 Abbreviations......Page 226 References......Page 227 Introduction......Page 234 Pyrrolidines and piperidines......Page 235 Pyrrolizidines......Page 240 Indolizidines......Page 242 Nortropanes......Page 243 Occurrence......Page 244 Isolation and structural determination......Page 245 Glycosidase Inhibitory Activity......Page 246 Mammalian Toxicity......Page 248 Introduction......Page 249 Biosynthesis of N-Linked Oligosaccharides......Page 251 Processing of N-Linked Glycoproteins and Effects of Glycosidase Inhibitors......Page 252 Introduction......Page 255 Degradation of Glycosphingolipids in the Lysosomes and Resulting Diseases......Page 256 Use of Glycosidase Inhibitors to Treat Lysosomal Lipid Storage Diseases......Page 257 Use of Inhibitors in Substrate Reduction Therapy......Page 260 Glycosidase Inhibitors in Diabetes Therapy......Page 261 Potentials for Therapy in Viral Diseases......Page 262 Abbreviations......Page 263 References......Page 264 Introduction......Page 270 N-Linked Glycosylation......Page 272 O-Linked Glycosylation......Page 273 Cytoplasmic O-GlcNAc......Page 274 C-Mannosylation......Page 275 Proteoglycans......Page 276 Chemical Approaches toward Understanding Protein Glycosylation......Page 277 Production of Homogeneous Glycoproteins......Page 278 Methods for Glycoconjugate Synthesis......Page 279 Expression of Homogeneous Glycoproteins......Page 282 Synthetic Modulators of Glycan-Protein Interactions......Page 286 Perturbation of Glycan-Processing Enzymes with Small Molecules......Page 289 Global Analysis of Protein Glycosylation......Page 291 Chemical Reporters of Protein Glycosylation......Page 292 FRET-Sensors of Protein Glycosylation......Page 297 Affinity Probes for Glycan-Binding Proteins......Page 298 Glycan Microarrays......Page 299 References......Page 300 Introduction......Page 306 Initiation Reaction......Page 307 Polyisoprenyl-phosphate N-acetylhexosamine-1-phosphate transferases......Page 308 Polyisoprenyl-phosphate hexose-1-phosphate transferases......Page 310 Elongation/Translocation/Polymerization......Page 311 O antigen translocase......Page 313 O antigen polymerase and the regulator of O antigen chain length......Page 314 Are the components of the Wzy-dependent pathway in a membrane complex?......Page 315 Parallels of the Wzy-dependent pathway and N-linked protein glycosylation......Page 316 Synthase-dependent pathway......Page 317 Ligation Reaction......Page 318 References......Page 319 Introduction......Page 324 Mucins......Page 325 Mucin-Type O-Glycans......Page 327 Functions of O-Glycans and Changes of O-Glycan Structures in Disease......Page 329 Biosynthesis of O-Glycans......Page 331 Structures and Mechanisms of Glycosyltransferases......Page 332 Initiation of O-Glycosylation......Page 333 Structures of Polypeptide GalNAc-Transferases......Page 334 Synthesis of Core 1......Page 335 Synthesis of Core 2......Page 336 Structure and Specificity of C2GnT1......Page 337 Role of Core 2 Structures......Page 339 Synthesis of Core 3......Page 340 Synthesis of Core 4......Page 341 Extension and Branching Reactions......Page 342 Extension GalNAc-Transferases......Page 343 beta4-Gal-Transferases......Page 344 Sialyltransferases......Page 345 alpha3-Sialyltransferases......Page 346 alpha6-Sialyltransferases......Page 347 alpha2-Fuc-Transferases......Page 348 alpha3/4-Fuc-Transferases......Page 349 Blood Group A and B Transferases......Page 350 Sulfotransferases......Page 351 Future Needs and Directions......Page 352 References......Page 353 Introduction......Page 360 Protein N-Glycosylation and O-Glycosylation at a Glance......Page 361 General Protein N-Glycosylation System in Campylobacter jejuni......Page 362 Flagellar O-Glycosylation in Campylobacter......Page 364 Flagellin glycosylation......Page 367 Type IV pilin glycosylation......Page 369 O-Glycosylation of Type IV Pilin in Neisseria......Page 372 Glycosylation of Autotransporters in Escherichia coli......Page 375 Protein O-Glycosylation in Gram-Positive Bacteria......Page 376 Protein O-Mannosylation in Mycobacteria......Page 377 Glycoengineering in Bacteria......Page 378 Glycoengineering in Escherichia coli Using the Bacterial N-Glycosylation System......Page 379 Glycoengineering in Escherichia coli Using Bacterial O-Glycosylation Systems......Page 380 Concluding Remarks......Page 383 Abbreviations......Page 384 References......Page 385 Introduction......Page 390 Arabinogalactan......Page 391 Phosphatidylinositol Mannoside, Lipomannan, Lipoarabinomannan, and Arabinomannan Structure......Page 392 Peptidoglycan Synthesis......Page 394 Biosynthesis of Arabinogalactan......Page 397 Biosynthesis of the Phosphatidylinositol Containing Phosphatidylinositol Mannosides, Lipomannans, and Lipoarabinomannans......Page 404 Mycobacterial Cell Envelope Ultrastructure......Page 406 References......Page 410 Heparan Sulfate and Heparin......Page 416 Localization of Proteoglycans......Page 417 Chain initiation......Page 419 Chain polymerization......Page 421 N-deacetylase/N-sulfotransferase......Page 422 Uronosyl 2-O-sulfotransferase......Page 424 Glycosaminyl 6-O-sulfotransferase......Page 425 Glucosaminyl 3-O-sulfotransferase......Page 426 Antiviral activity......Page 427 The lectican family......Page 428 Physiological Importance of Chondroitin Sulfate and Dermatan Sulfate......Page 429 Other Glycosaminoglycans......Page 430 Abbreviations......Page 431 References......Page 432 Biochemistry and Molecular Biology of Glycogen Synthesis in Bacteria and Mammals and Starch Synthesis in Plants......Page 437 Introduction......Page 438 Plant Starch......Page 439 Glycogen Synthesis in Bacteria......Page 440 Starch Synthesis in Plants and Algae......Page 441 Molecular weight and subunit structure......Page 442 Reaction mechanism......Page 443 Activators and Inhibitors of ADP-Glc PPase......Page 444 Effect of Activators and Inhibitors on ADP-Glc PPase Kinetics......Page 447 Experimental Evidence Supporting the Role of ADP-Glc PPase in the Regulation of the Biosynthesis of Bacterial Glycogen and Plant Starch......Page 448 Plant ADP-Glc PPases Can Be Activated by Thioredoxin......Page 451 Bacterial systems......Page 452 Substrate sites......Page 453 Activator sites......Page 454 Properties and functions of the small and large subunits of higher plant ADP-Glc PPases......Page 455 Crystal Structure of Potato Tuber ADP-Glc PPase......Page 459 Substrate and Catalytic Sites......Page 460 Reversibility of the Glycogen Synthase Reaction......Page 462 Soluble starch synthase I......Page 463 Starch synthase II......Page 464 Starch synthase IV......Page 466 Double mutants of the soluble starch synthases......Page 467 Starch synthases bound to the starch granule......Page 468 Isolation of the waxy protein structural gene......Page 469 Further studies of GBSS and isoforms; their involvement in both amylopectin and amylose synthesis......Page 470 Plant and Algal Branching Enzymes; Characterization of Isozymes......Page 472 Genetic Studies on Branching Enzyme-Deficient Mutants......Page 474 Isolation of cDNA Clones Encoding the Branching Enzyme Isozyme Genes......Page 475 Branching Enzyme Belongs to the alpha-Amylase Family......Page 476 Isoamylase......Page 477 Genetic Regulation of Bacterial Glycogen Synthesis......Page 478 UDP-Glucose Pyrophosphorylase......Page 480 Branching Enzyme......Page 481 Glycogenin......Page 482 Genetic evidence indicating that glycogenin is required for glycogen synthesis......Page 483 Regulation of Glycogen Synthase by Phosphorylation - Dephosphorylation......Page 484 In vitro studies......Page 486 In vivo studies......Page 487 Inactivation of glycogen synthase kinase-3......Page 489 References......Page 490 Introduction......Page 500 Structures and States of Aggregation......Page 501 Structural Studies......Page 504 Solid-State 13C NMR Spectra and the Two Forms of Native Cellulose Ialpha and Ibeta......Page 505 The Need for a New Paradigm......Page 511 Raman Spectroscopy......Page 512 Raman and Infrared Spectra......Page 516 Solid-State 13C NMR Spectra......Page 518 Electron Microscopic Studies......Page 520 Computational Modeling......Page 521 Polymorphy in Cellulose......Page 523 Chemical Implications of Structure......Page 524 Cellulose Structures in Summary......Page 527 Solvents......Page 528 Derivatization......Page 530 Esterification......Page 531 Etherification......Page 533 Oxidation......Page 536 Thermal degradation......Page 538 Chemical and Enzymatic Syntheses of Cellulose......Page 540 References......Page 543 Vascular Plant Lignification: Biochemical/Structural Biology Considerations of Upstream Aromatic Amino Acid and Monolignol Pathways......Page 547 Lignification: A Pivotal Role in Vascular Plant Evolution......Page 548 Biochemistry of Phenylalanine and Tyrosine Formation in Vascular Plants: The Entry Point to Phenylpropanoid Metabolism and to Lignification......Page 549 The Previous Enigma of Arogenate and/or Prephenate Dehydratases in Plants: The Role of Arogenate Dehydratase......Page 551 The Enigma of Prephenate and/or Phenylpyruvate/p-Hydroxyphenylpyruvate Aminotransferases in Plants......Page 555 Product feedback control......Page 557 Transcription......Page 559 Bacterial Prephenate Dehydratases and Plant Arogenate Dehydratases: A Structural Biology Comparison via Homology Modeling......Page 560 HAL, PAL, and TAL: Discovery of the MIO prosthetic group......Page 563 Putative catalytic mechanisms for HAL, PAL, and TAL......Page 566 HAL and PAL: Proposed Tyr loop-in model for lsquobreathing’ motion for substrate access......Page 568 The molecular basis of PAL and TAL substrate versatility......Page 569 Hydroxycinnamoyl CoA:Shikimate/Quinate Hydroxycinnamoyltransferase......Page 570 Cinnamate 4-hydroxylase......Page 575 Ferulate 5-hydroxylase......Page 577 Catalysis......Page 578 3D Structures......Page 580 Conformational changes during catalysis: Relevance to 4CL?......Page 582 Mode of action of catalysis......Page 585 Protein interactions with pyrophosphate leaving group......Page 586 O-Methyltransferases in the monolignol pathway: Discovery of lsquoCOMT’ and lsquoCCOMT’ proper......Page 587 S-COMT 3D structure......Page 588 3D structure of CCOMT......Page 590 Structural comparisons of S-COMT and CCOMT and catalytic mechanisms......Page 591 3D structure of lsquoCOMT’......Page 592 Cinnamoyl CoA Reductase......Page 593 Cinnamyl Alcohol Dehydrogenase: Comparison to Horse Liver Alcohol Dehydrogenase......Page 596 CAD......Page 597 Comparison of AtCAD5 with poplar lsquoSAD’ and yeast lsquoCAD’......Page 598 CAD catalysis and putative proton relay......Page 599 References......Page 601 Introduction......Page 611 The Naming Convention......Page 612 Biosynthesis......Page 614 Flavans......Page 616 Flavan-3-ols......Page 619 Flavan-4-ols......Page 626 Proanthocyanidins......Page 628 Procyanidins (3,5,7,3’,4’-pentahydroxylation)......Page 629 Propelargonidins (3,5,7,4’-tetrahydroxylation)......Page 646 Proguibourtinidins (3,7,4’-trihydroxylation)......Page 648 Promelacacinidins (3,7,8,3’,4’-pentahydroxylation) and proteracacinidins (3,7,8,4’-tetrahydroxylation)......Page 650 Probutinidins (7,3’,4’-trihydroxylation)......Page 651 A-Type Proanthocyanidins......Page 653 Conformation of Proanthocyanidins......Page 657 Effects of Proanthocyanidins on Human Health and Nutrition......Page 659 References......Page 660 Introduction......Page 668 2’-OMe Modification Effects on RNA Duplex Stability......Page 670 2’-O-Methyl Modifications in Thermophilic tRNA......Page 671 2’-O-Methyl Modification in Ribosomal RNA......Page 672 Fundamental Properties of psi Modification......Page 673 psi in Small Nuclear RNA......Page 674 psi in Helix 69 of 23S rRNA......Page 675 2-Thio, 5-X-Modified Uridines - s2U, mnm5s2U, and mcm5s2U......Page 677 Nucleosides that Form Rare Tautomers - cmo5U and taum5U......Page 679 Modified Cytidines - Ac4C, fhairsp5C, Ac4Cm, and fhairsp5Cm......Page 680 The Lysine-Modified Nucleoside, Lysidine......Page 681 Purine Modifications - m1G, i6A, t6A, yW, and Q......Page 682 Summary and Future Prospects......Page 683 References......Page 684 Introduction......Page 688 Methylation on Carbon......Page 689 Methylation on Tertiary Nitrogen......Page 692 Methylation on Primary Nitrogen......Page 695 Methylation on Oxygen......Page 698 Thiolation......Page 701 Selenation......Page 704 Deamination......Page 705 Adenosine Deamination (A to I)......Page 706 Cytidine Deamination (C to U)......Page 709 Dimethylallylation......Page 710 Lysidine Formation......Page 713 Reduction/Oxidation......Page 714 tRNA-Guanine Transglycosylase......Page 717 Pseudouridine Synthase......Page 723 Queuosine and Derivatives......Page 728 Wyosine and Derivatives......Page 732 Conclusions and Perspectives......Page 736 Abbreviations......Page 738 References......Page 739 Introduction......Page 747 Transcriptional Attenuation......Page 748 Translation Initiation......Page 749 Regulatory Signals......Page 750 Mebabolite-Binding Riboswitches......Page 752 RNA Thermosensors......Page 754 RNA-Binding Riboswitches......Page 755 Composite Riboswitches......Page 756 Single-domain riboswitches......Page 757 Riboswitches and Gene Identification......Page 758 Natural Riboswitches as Genetic Control Elements for Heterologous Gene Expression......Page 759 Perspectives and Future Directions......Page 760 References......Page 761

This work presents a definitive interpretation of the current status of and future trends in natural products-a dynamic field at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids, and enzymes. With more than 1,800 color figures, Comprehensive Natural Products II features 100% new material and complements rather than replaces the original work (©1999).

• Reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine
• Stimulates new ideas among the established natural products research community-which includes chemists, biochemists, biologists, botanists, and pharmacologists
• Informs and inspires students and newcomers to the field with accessible content in a range of delivery formats
• Includes 100% new content, with more than 6,000 figures (1/3 of these in color) and 40,000 references to the primary literature, for a thorough examination of the field
• Highlights new research and innovations concerning living organisms and their distinctive role in our understanding and improvement of human health, genomics, ecology/environment, and more
• Adds to the rich body of work that is the first edition, which will be available for the first time in a convenient online format giving researchers complete access to authoritative Natural Products content

v. 1: Natural Products Structural Diversity-I Secondary Metabolites: Organization and Biosynthesis. v. 2.: Natural Products Structural Diversity-II Secondary Metabolites: Sources, Structures and Chemical Biology. v. 3.: Development & Modification of Bioactivity. v. 4.: Chemical Ecology. v. 5.: Amino Acids, Peptides and Proteins. v. 6.: Carbohydrates, Nucleosides & Nucleic Acids. v. 7.: Cofactors. v. 8.: Enzymes and Enzyme Mechanisms. v. 9.: Modern Methods in Natural Products Chemistry.