Index

A-, 338 ALG9,165 ABO blood group system, 330 ALGlO,168 and cloning, 338 genetic basis of, 22 B-transferase, 338 activated oligosaccharides bacterial S-Iayers in glycopeptide synthesis, 466, 470 glycosylation in, 439 2-aminoethylphosphonate bacterial toxins in invertebrate glycoproteins, 420 and glycosylation, 413 anomer, 5 biological macromolecules formal defmition of, 6 the four groups of, 2 Hudson definition of, 6 bird's nest soup, 16 anomeric carbon blood group antigens, 22 in synthesis, 459 and cancer, 23 anomeric effect, 8 prognostic value of, 23 anomeric oxygen exchange reactions, blood typing, 22 460,461 ABO system of, 22 anomeric oxygen-retaining reactions, 460, Lewis system of, 22 464 Bombay blood group, 331, 336, 348 antennae Bombay phenotype, 22 definition of, 10 branch specificity, 93 J3-arabinofuranose in plants, 418 caeruloplasmin, 23 asialoglycoprotein receptor, 494 calnexin, 54, 182 asparagine-linked glycosylation calreticulin, 54, 182, 188 ALGI, 158 capillary electrophoresis, 457 ALG2,161 carbohydrate metabolism, 1, 17 ALG3,165 Carbohydrate-Deficient Glycoprotein ALG5,167 Syndrome (COGS) Type 1, 152 ALG6,168 Carbohydrate-Deficient Glycoprotein ALG7,155 Syndrome (COGS) Type II, 226 ALGB,168 500 Index

Carbohydrates; See a/so oligosaccharides deoxymannoj irimycin, 191 as molecules with key biological deoxynojirimycin, 184 functions, 3 dietary sugars, 1 biology of, 2 disaccharides covalent attachment to protein, 17 structural determination of, 17 definition of, 4 DNA,1 in bacterial and viral infection, 4 dolichol, 149 in biology, re-evaluation of, 4 in the biosynthesis ofglycoproteins, in cancer and metastasis, 4 28 in signalling, 3 dolichol cycle, 99 optical rotation of: See mutarotation dolichylphospho-13-glucose (Dol-P-Glc) polymerisation of, 6 synthetase, 167 shorthand nomenclature of, 12 dolichylphospho-13-mannose (Dol-P· structure of, 5 Man) synthetase, 163 terminology of, 12 donor substrates castanospermine, 184 for , 88 chaperones, 182 drug targeting, 493 chemical synthesis ofglycosides, 459 13-elimination, 17 Chinese hamster ovary cells endoglycosidases /dlD mutant, 286 in structural determination of Lecl mutant, 217 oligosaccharides, 30 Lec4 mutant, 232 endomannosidase, 186 Lec9 mutant, 150 and glycoprotein folding, 55 LECII mutant, 364 enzymatic peptide ligation LEC 12 mutant, 364 in glycoside formation, 481 Lec15 mutant, 164 enzymatic synthesis Lec23 mutant, 185 automated, 479 Lec35 mutant, 164 ofglycosides, 475 chondroitin sulphate structural determination of, 17 Commission designations of, cluster effects, 72 15 CMP-Neu5Ac epidermal growth factor-like domains biosynthesis, 374 glycosylation of, 308 hydroxylation, 375 epimer CMP-Neu5Gc, 375 definition of, 6 collagen erythropoietin glycosylation of, 315 as a glycodrug, 495 core structure O-linked glycosylation of, 283 definition of, 10 expression cloning, 32 CWH41,184 in S. cerevisiae, 430 Fischer projection, 6 cyclic acetals flipping carbohydrates as, 8 and the dolichol cycle, 100 cyclic hemiacetals dolichyl-oligosaccharide, 161 carbohydrates as, 5 fluorescence energy transfer experiments and glycoprotein folding, 57 deglycosylation Francis inhibitor, 21 methods for, 52 Index 501 a 1,3-fucose galactobiosides in plant glycoproteins, 414 as inhibitors ofbacterial al,6-fucosylation haemagglutination, 27 in invertebrates, 419, 420 galactofuranose in mammals, 236 in parasite glycoproteins, 424 galactomannans cloning of, 22 in S. pombe, 433 a 1,2- genes galactosaemia, 1 cloning of, 32 a-galactose human, 333 in mammals, 340 mouse, 337 in plants, 418 rabbit, 337 galactosyItransferases al,3-fucosyItransferases; See also and glycosaminoglycan biosynthesis, Fuc-TIll, etc. 312 in humans, 348 and N-linked glycosylation, 238 in invertebrates, 419, 420 and O-Iinked glycosylation, 296 in parasites, 426 al,3- (B­ in plants, 416 transferase), 23,338,341 a 1,3-fucosyltransferase genes human pseudogenes, 341 avian, 364 substrate specificity, 342 bovine, 365 pI,3- chimpanzee, 365 and mucin-type glycosylation, 295 He/icobacter pylori, 365 and N-Iinked glycosylation, 250 human pl,4-galactosyltransferase,238 FUT3,351 and poly-LacNAc biosynthesis, 369 FUT4,354 and rheumatoid arthritis, 248 FUT5,355 and a-lactalbumin, 239 FUT6,357 branch preference, 239 FUT7,359 cDNA cloning, 240 rodent cDNAs,32 FUT4,362 cell surface, 249 FUT7,363 cell surface localisation, 241 a 1,3/4-fucosyltransferase: See Fuc-TIll Golgi localisation, 245 a 1,4-fucosyltransferase in the synthesis oflactose, 32 in plants, 417 knock-out, 249 al,6-fucosyltransferase, core multiple genes, 243 mammalian, 236 post-translational modifications, 246 cDNA cloning, 237 substrate binding sites, 245 Fuc-TIII,350 substrate specificity, 239 Fuc-TIV, 354 galectins, 24 Fuc-TV,355 pI,4-GaINAc transferase Fuc-TVI,357 in invertebrates, 421 Fuc-TVII,359 in mammals, 385 furanose, 6 gangliosides,380 FUTI: See H (al,2-fucosyltransferase) Gaucher's disease, 480, 494 GlcNAc-l-phosphodiester a-N-acetyl- glucosaminidase galactobiose epitope, 23, 340 and lysosomal marker biosynthesis, and xenotransplantation, 342 391 502 Index

GlcNAc-l-phosphotransferase glucosidase II and lysosomal marker biosynthesis, and glycoprotein folding, 54 389 glucosidases 1 and II, 184 GlcNAc-TI glucosylation, 413 cDNA cloning, 219 genomic localisation, 220 dolichyl-Iinked substrate, 168 Golgi localisation, 220 glycoprotein substrate, 189 in invertebrates, 419 f31,3-glucuronyltransferases in mammals, 217 and glycosaminoglycan biosynthesis, in plants, 416 312 knock-out, 221 and HNK-l epitope biosynthesis, 387 substrate specificity, 218 G1yCAM-l,366 G1cNAc-TIl, 419 biosynthesis of, 285, 362 cDNA cloning, 226 mucin-type oligosaccharides of, 360 in invertebrates, 419, 421 sulphation of, 300 in mammals, 225 glycation, 412 in plants, 416 and the Amadori rearrangement, 412 substrate specificity, 225 and the Maillard reaction, 412 GlcNAc-TIll, 227 glycoamidases and metastasis, 229 in structural determination of cDNA cloning, 228 oligosaccharides, 30 G1cNAc-TIV,230 glycobiology, 33 cDNA cloning, 230 coinage ofthe term, 2 G1cNAc-TV glycoconjugates and cancer, 31 and cancer, 30 and metastasis, 233 coinage ofthe term, 2 and the Warren-Glick phenomenon, definition of, 2 233 hierarchical classification of, 13 cDNA cloning, 232 glycodrugs, 494 genomic localisation, 233 glycoforms, 33, 457 substrate specificity, 231 impact on drug design, 34 GlcNAc-TVI,235 isolation of, 457 f31,3-GlcNAc transferase synthesis of, 457 and poly-LacNAc biosynthesis, 369 varying properties of, 34 core 3 glycogen and mucin-type glycosylation, 300 as a glycoprotein, 35 f31,4-GlcNAc transferase catabolism, 17 cloning ofthe invertebrate enzyme, glycohazards, 411 421 glycoimmunology,4 f31,6-G1cNAc transferase glycolipids, 17 and poly-LacNAc biosynthesis, 369 glycopathology, 4, 31 core 2 glycophorin, 21 and mucin-type glycosylation, 295 glycoprotein, 1 core 4 definition of, 13 and mucin-type glycosylation, 301 as a mixture ofglycoforms, 33 GLS2 glycosaminoglycans, 309 in S. cerevisiae, 430 glycoscience,4, 15 o-glucose glycosidase inhibitors, 181 structural determination of, 16 Index 503 glycosidases, 4, 33, 85 GPI membrane anchors and the cleavage ofglycosides, 89 biosynthesis, 124 endoglycosidases, 90 in parasites, 422 exoglycosidases, 90 glycoamidases, 90 H (al,2-fucosyltransferase) gene, 331 in glycoside fonnation, 479 cloning, 333 trans-glycosidases, 90 polymorphisms, 335 glycosides haemagluttination, 19 shorthand nomenclatures for, 8 Helicobacter pylori, 284, 352 synthesis of, 458; See also Chapter 9 al,3-fucosyltransferases of, 365 thennodynamic barrier to fonnation HEMPAS,223 of, 87 hepatic receptor protein, 24 glycosidic bonds: See glycosides J3-hexosaminidase glycosidic linkages: See glycosides in invertebrates, 419, 420 glycosyl acceptor, 8 in mammals, cytosolic, 307 in synthesis, 459 HNK-I epitope,387 glycosyl donor, 6 H-transferase (a1,2-fucosyltransferase), in synthesis, 459 334 glycosylamino acids Hudson's rule, 6 in glycopeptide synthesis, 466 violation of, 6 glycosylation human chorionic gonadotropin, 35 in insects, 418 hydrazinolysis, 29 in invertebrates, 418 hydroxylysine in mammals: See individual enzymes glycosylation of, 315 in parasites, 422 hypennannosylation in plants, 414 in yeast and fungi, 427 in snails, 421 in yeast and fungi, 427 I-cell disease, 390 glycosylation engineering, 482 immunogenic oligosaccharides, 411, 417 glycosylation mutants, 29 immunoglobulin G, 31 glycosylphosphatidylinositol membrane influenza virus, 19 anchors, 74 invariant region ofoligosaccharides: glycosyltransferases, 4, 33, 85 See core structure, definition of blood-group associated, 22 defective alleles, 22 Jaeken syndrome, 152 discovery of, 28 gene cloning, 32 heterologous expression of, 32 kifunensine, 192 in glycoside fonnation, 475 kin recognition in synthesis, 32 ofglycozymes, 91 purification of, 31 Koenigs-Knorr procedure, 461 structure/function relationships and, Kre2plMntip 87 in S. cerevisiae, 432, 436 transcriptional regulation of, 31 KRE5 glycotechnology, 4, 411 in S. cerevisiae, 428 glycotype, 33, 85 KTR2,432 glycozymes, 85 KTR3,432 Golgi retention signals, 91 KTR4,432 Go-NaGa,93 KTR5,433 KTR6,433 504 Index

KTR7,433 mannosidase, ER, 190 cloning of, 193 LacdiNAc sequences, 121 a 1,2-mannosidase, 190 in invertebrate glycosylation, 419 in invertebrates, 419 in mammals, 385 in yeast, 430 LacNAc,120 p-mannosides a-lactalbumin, 239 synthesis of, 464 lectins, 64, 494; See also selectins mannosylation animal,24 C-mannosylation oftryptophan, 414 as analytical tools, 24 in neural tissue, 414 bacterial, 26 I: See pl,4­ C-type,24 mannosyltransferase definition of, 24 II, III, IV and V, hepatic, 24, 34 159 I-type, 24 mannosyltransferases VI, VII, VIII and P-type,24 IX, 165 viral,21 a I,6-mannosyltransferase Leloir-type glycosyltransferases, 88 in yeast, 430 in glycosidic bond formation, 475 Pi ,4-mannosyltransferase, 158 Leukocyte Adhesion Deficiency (LAD) cloning in slime moulds, 439 Type II, 348 methylation Lewis histo-blood group antigens, 22, 344 ofinvertebrate glycoproteins, 422 Lewis transferase: See Fuc-TIll methylgalactose Lewisa (Lea), 27, 344 in invertebrates, 421 Lewisb (Leb), 344 microheterogeneity, 33, 457 Lewisx (LeX), 27,344, 425 and glycoprotein function, 76 LewisY (LeY), 344 generation of, 213 lysosomal targeting, 388 mnnmutants in S. cerevisiae, 431 MNSJ M2MT-I in S.cerevisiae, 431 in S. cerevisiae, 430 M~-mannosidases, 193 monoclonal antibodies mannans, 427 as analytical tools, 27 mannose monosaccharides as an inhibitor ofbacterial chemical coupling of, 6 haemagglutination, 26 classification of, 6 mannose, 6-phosphate definition of, 5 lysosomal, 388 repertoire in Nature, 10 mannosidase I, 190 MUCI (mucin), 287, 297 cloning of, 194 mucins, 15,58 mannosidase II, 221 as inhibitors ofhaemagglutination, 21 cDNA cloning, 222 early definition of, 15 in invertebrates, 419 mucin-type glycosylation, 282 in mammals: See Chapter 4 and amino acid consensus sequence, in plants, 416 284 knock-out, 224 core 1,295 mannosidase IIX, 223 core 2, 295 mannosidase III, 224 and disease, 297 core 3,300 Index 505

core 4,301 in mammals, 97 elongation of, 294 in plants, 122,414 initiation of, 286 in prokaryotes, 440 mucopolysaccharides, 2 in yeast and fungi, 117,427 mutarotation, 5 N-linked oligosaccharides complex type, 97 N-acetyIgalactosarninyltransferases definition of, 8 in mammalian LacdiNAc synthesis, hybrid type, 97 385 oligomannose type, 97 in mucin-type glycosylation: See paucimannose in insects, 120 ppGalNAc trimannosyl core, 97 131,4-N-acetylgalactosaminyltransferases vacuole type in plants, 122 and chondroitin sulphate biosynthesis, NoGo-Go,93 313 nomenclature N-acetylglucosaminylphosphotransferase for glycozymes, 90 and dolichyl-linked oligosaccharides, non-Leloir-type glycosyltransferases, 88 154 in glycoside formation, 475 and lysosomal marker biosynthesis, non-secretors, 22 389 nucleoside phosphate sugars: See N-acetylglucosaminyltransferase, 216 glycosyl donors N-acetylglucosarninyltransferase II: See nucleotide sugars GIcNAc-TII in glycosidic bond formation, 476 N-acetylglucosaminyltransferase III: See GlcNAc-TIll oem N-acetylglucosaminyltransferase IV: See in S. cerevisiae, 430 G1cNAc-TIV O-fucosylation, 308 N-acetylglucosaminyltransferase V: See O-fucosyltransferase, 309 GlcNAc-TV O-GlcNAc transferase, 307 N-acetylglucosaminyltransferase VI: See O-GlcNAcylation, 306 G1cNAc-TVI as a regulatory modification, 62 a 1,3-N-acetyIglucosarninyltransferase oligomannose (A-transferase), 338 in plant glycoproteins, 414 a 1,4-N-acetylglucosaminyltransferase oligosaccharides; See also carbohydrates and heparan sulphate biosynthesis, and cell-cell adhesion, 64 314 and cell-ECM adhesion, 71 N-butyldeoxynojirimycin, 184 and glycoprotein catabolism, 72 neighbouring group participation and glycoprotein conformation, 58 in glycosylation reactions, 463, 464 and glycoprotein folding, 54 neoglycoproteins and glycoprotein function, 61 synthesis of, 466, 471 and glycoprotein secretion, 54 neural cell adhesion molecule (NCAM) and glycoprotein targeting, 72 sialylation, 380 and glycoprotein trafficking, 72 neuraminic acid and lysosomal targeting of structural determination of, 17 glycoproteins, 72 neuraminidase, 21 and metastasis, 24 N-Iinked glycosylation and molecular recognition, 74 in bacteria, 129 and protective roles, 60 in birds, 97 as mediators ofhormonal signals, 35 in insects, 120 biological roles, 49 506 Index

bisected, 34 ovalbumin branching of, 10 as a glycoprotein, 17 definition of, 5 methods ofshorthand notation, 14 patents methods to study biological roles, 52 glycoforms and, 494 multiplicity of, 10 3'-phosphoadenosine-5'-phosphosulphate N-Iinked, branching of, 213 (pAPS), 386 'non-specific' roles, 50 phosphoglycosylation O-Iinked, mammalian, 281 in parasites, 425 similarity of, 10 phosphomannomutase, 152 'specific' roles, 50 photosynthesis, 2 structural determination of, 28 pituitary glycoproteins synopsis ofshorthand nomenclature, biosynthesis, 385 15 plasminogen activator, 494 oligosaccharyltransferase, 170 PMTgenes acceptor substrate, 176 in S. cerevisiae, 437 as a multi-subunit complex, 170 poly-LacNAc: See poly-N-acetyl­ dolichyl-Iinked substrate, 175 lactosaminoglycans in parasites, 423 poly-N-acetyllactosaminoglycans, 369 mammalian, 173 polysaccharides, I Dadl,174 definition of, 5 OST48,173 ppGalNAc transferases, 285 ribophorins, 173 GaINAc-Tl, 290 mechanisms, proposed, 178 GaINAc-n, 292 subunits, genes GalNAc-T3, 293 OSTl,l72 GalNAc-T4,293 OST2,172 localisation, 285 OST3,172 substrate specificity, 286 OST4,172 protecting groups, 8, 462 OST5,172 in glycosylation reactions, 462 SIT3,173 protein glycosylation SWPl,l72 and cancer, 30 WBPl,171 examples of, 8 O-Iinked GIcNAc in non-mammalian organisms, 411 in mammals, 306 in the nucleus and cytoplasm, 35 in parasites, 424 routes to, 87 O-Iinked glycosylation types of, 19 in birds, 112 proteoglycans, 2, 71,309 in insects, 122 biosynthesis, 127 in mammals, 112 P-selectin glycoprotein ligand-I: See in plants, 123,418 PSGL-I in prokaryotes, 440 PSGL-I,367 in yeast and fungi, 120,436 mucin-type glycosylation of, 299 non-mucin type in mammals, 114 pyranoses, 6 O-linked oligosaccharides six-membered ring formulation of, 16 definition of, 8 'one linkage, one enzyme' hypothesis, 89 receptor-destroying enzyme, 21 al,3/4-fucosyltransferase as an reducing sugars, 5 exception, 89 reducing terminus, 5 Index 507 regioselectivity in synthesis, 459 homology, 377 rhamnose, 425 a2,3-sialyltransferases, 378 rheumatoid arthritis, 31 and mucin-type glycosylation, 301 and glycoproteins, 59 and N-Iinked glycosylation, 258 and 131,4-galactosyltransferase, 248 a2,6-sialyltransferases,378 ribonuclease B, 34 and mucin-type glycosylation, 304 ribophorins, 173 and N-linked glycosylation, 251 ribose a2,8-sialyltransferases,380 as a building block ofDNA, 2 siglecs: See sialoadhesins Rosanoff nomenclature, 6 site-directed processing, 95 site-specific topological modulation, 95 saccharides solid-phase synthesis definition of, 4 ofglycopeptides, 467 schistosomiasis ofoligosaccharides, 460 and glycosylation, 425 ST3Gal I, 302, 378 Se (al,2-fucosyltransferase) gene, 332 ST3Gai II, 302, 304, 378 polymorphisms, 335 ST3Gai III, 259, 378 secJ8 ST3Gai IV, 260, 378 in S. cerevisiae, 438 ST6Gai I, 252, 379 secretors, 22 and acute-phase response, 258 selectins, 24, 65 branch preference, 253 and leukocyte rolling, 69 cDNA cloning, 254 and trafficking ofmacrophages, 24 genomic organisation, 255 E-selectin, 68, 347 Golgi localisation, 257 L-selectin, 67, 347 recombinant, 257 P-selectin, 68, 347 substrate specificity, 253 topology, 67 ST6GaiNAc 1, 305, 379 selectins, ligands ST6GaiNAc II, 305, 379 for E-selectin, 366 ST6GaiNAc III, 305, 379 for L-selectin, 366 ST8Sia 11,381 for P-selectin, 366 ST8Sia III, 383 Se-transferase (a1,2-fucosyltransferase), ST8Sia IV, 383 335 Stage-Specific Embyonic Antigen-l showdomycin, 158 (SSEA-l), 27 sialic acid, 373 stereoselectivity structural determination of: See in glycosylation reactions, 463 neuraminic acid in synthesis, 459 sialoadhesins, 24 straight-chain B antigen, 23 sialylation, 373 and transplantation, 23 ofmucin-type oligosaccharides, 301 sugars: See carbohydrates and ofN-linked oligosaccharides, 251 oligosaccharides sialyl-Lewis3 (sialyl-Le3), 346 sulphotransferases, 386 x X sialyl-Lewis (sialyl-Le ), 346, 424 and glycosaminoglycan biosynthesis, enzymatic synthesis of, 477 314 sialylmotifL,377 swainsonine, 29, 221 sialylmotifS,377 sialylmotifVS,378 thapsigargin, 191 tissue plasminogen activator, 34 508 Index

Tn antigen, 113 transporter proteins in glycoprotein biosynthesis, 88 trans-sialidase in parasites, 424 trichloroacetimidate reaction, 461 trimming ofGIc3M~GlcNAc2 181 tunicamycin, 29, 54, 155 ' tunicamycin resistance gene (TRG, ALG7),155 Type II membrane topography, 87 tyvelose in parasite glycoproteins, 426

uridine diphosphate sugars, 27

variable region ofoligosaccharides: See antennae, definition of Vibrio cho/erae, 21 viruses haemagglutinating, 21

Warren-Glick phenomenon, 30, 233 wine-making, 1 Wiskott-Aldrich immunodeficiency syndrome, 298

xenotransplantation, 411, 495 X-ray crystallography, 497 xylose in plant glycoproteins, 414 and glycosaminoglycan biosynthesis, 310 131,2-xylosyltransferase in plants, 416

fURI,432