Abzymes 162 Acetoacetate Decarboxylase 16 Stereochemistry

Index

Abzymes 162 Aldolases 126 Acetoacetate decarboxylase 16 Alko process 332 stereochemistry 19 Allylic pyrophospJiates 291 Acetoin 77 Alum'inium 252 Acetyl choline receptor 369 Alzheimer's disease 207, 252 Acetyl cholinesterase 252 Aminoacid oxidase 68 Acid catalysis in glycoside hydrolysis Aminoacids, unnatural, synthesis 119 331 Amylases 309 et seq. Acid proteases 193 a-amylase, structure 314 mechanism of action 194 a-amylases 310 Acids, hard and soft 230 a-amylases, genes for 313 Acylases in industrial production of a-amylases substrate interaction with L-aminoacids 117 313 Acylation, selective with crown ether l3-amylases, genes for 313 complexes 143 Anaemia 233,248 Addition reactions, micellar control of Analogy in synthetic uses of enzymes 146 106 Adcoosine triphosphate (ATP) Angiotensin converting enzyme 5, 189 recycling 102, 133 Angiotensin converting enzyme, AIDS 249 inhibitor synthesis 118, 127 Alcohol dehydrogenase 100 Antibodies, catalytic 45,162,362 horse liver 108 Antibodies 353,360 in organic solvents 155 Anticancer drugs 176,228 models for 52 et seq. Antimalarial agents 173 reactivity extension possibilities 152 Antitumour activity 249 yeast, genetic engineering of 157 Apolipoprotein B 3~3 Aldol reactions 125 Arthritis, rheumatoid 229,253 376 Index

Ascorbic acid 108 ~-blockers, synthesis 124 Aspartase in industrial synthesis of Blood group determinants 126 aspartic acid 114 Blood pressure, control of 189 Aspartate aminotransferase, site Boranes, chiral 104,129 directed mutagenesis of 357 Borohydride, complex reagents 129 Aspergillus oryazae acylase in amino Brewing 332 acid manufacture 120 Bnljnsted relationship 28 Asymmetric Michael addition, crown ether complexes 143 Cadmium 239,251 Asymmetric oxidation by HLADH 109 Caeruloplasmin 230,233,238,239,241 Asymmetric oxidations 70 Calcium 250 Asymmetric reduction in protein structure 339 byHLADH 108 Calixarenes 136 by nicotinamide coenzyme models 60 Calmodulin 250 Asymmetric synthesis 3 Calsequestrin 250 Atherosclerosis 200,363 Cancer 234,230 Atomic absorption spectrometry 261 chemotherapy 133 Augmentin 185 Candida cyclindraceae lipase (CCL) 117 Auranofin 253 Captopril, synthesis 127 Carbapenems 186 ~-barrel 358 Carbohydrates, acylation using lipases Bacteriophage 361,360 155 Barley 332 Carbon acids, proton transfer from 27 Benzene cis-glycol 158 Carbon-carbon bond formation by Benzene dioxygenase 158 enzymes 125 Benzoin 77 Carboxypeptidase 231,248 Beta galactosidase 319 Carboxypeptidase A 14,190 Beta methylaspartase, stereospecific Carboxypeptidases, penicillin binding addition catalysed by 115 182 Bilaphos, biosynthesis of 275 Catalysis Bile acid sequestrants 200 acid 54 Binaphthyl, chiral 117,129,143 acid-base 26 Binding energy in enzymic catalysis 363 and association Binding sites 24 by enzymes multiple 40 binding energy in 357 Bioavailability of drugs 200 mechanism 8 et seq. Biochemical differences between theoretical treatments of 22 et seq. , species 173 356 Biological technologies 98 by metal ions 52 Biomimetic chemistry 42, 133 concepts 9 Biosynthesis intramolecular 55 natural products 265 et seq. non-covalent interactions 56 catecholamines 172 synthetic 42 Biosynthetic enzymes 267 et seq. Catalytic antibodies 45,162 Biosynthetic pathways 98 Catalytic efficiency of enzymes 31 genetic manipulation of 108 Catecholamines 172 Biotin 34 Cefoxitin 185 Bi-product inhibitors 191 Cell surface receptors 367 Blocked mutants in biosynthetic studies Cell-free system 283 for generating flavour compounds 347 ~-blockers 97 in biosynthetic studies 270, 275 Index 377

Cellulases Coupled enzymes in cofactor recycling fungal 327 101 molecular studies of 329 Covalent bonds, in selectivity of Cellulose 321 biomimetic systems 138 hydrolysis 326 Crown ethers 136,142 et seq. Celluloses, structure 320, 323 in nicotinamide coenzyme models 59, Cephalosporin 187 61 biosynthesis of 269 Crystallin 360 Cephalosporin A, as an elastase Curtin-Hammett principle 15 inhibitor 215 Cyclodextrins 42, 135, 141 et seq., 320 Cephalosporium acremonium, in nicotinamide coenzyme models 58 isopenicillin N synthetase 160 pyridoxal models 81 Cheese flavour development 346 Cycloguanil 174 Cheese making 338 et seq. Cyclophanes Cheese ripening, accelerated 344 in flavin models 71 Chemically modified enzymes 151 in nicotinamide coenzyme models 60 Chemiluminescence 74 in pyridoxal models 81 Chemo-enzymatic synthesis 164 Cytochrome P-450 149,236 Chirality 20 Chlorination Daunosamine 107 anisole 141 Deazaflavins 63 phenol, biomimetic in micelles 146 Debranching of polysaccharides 317 steroids 138 Decarboxylation, by thiazolium salts 77 Cholesterol biosynthesis, inhibitors of Dehydrogenases, in chiral intermediate 200 et seq. preparation 116 Cholestyramine 200 Diaminopyrimidines 173 Chorismate mutase 163 Diamond lattice model 109 Choroperoxidase 150 Diels-Alder reaction 142 Chromium 244 Diet, human 318 Chymosin 340 Diffusion and reaction rates 32 Chymotrypsin 108 Dihydrofolate reductase in organic solvents 153 in synthesis 131 Circular dichroism 258 inhibitors of 173 et seq. Claisen rearrangement, catalytic Dihdyrofolate reductases, inhibitor antibodies 163 resistant 180 Clavulanic acid 185,275 Dipodascus uninucleatus reductase 128 Clofibrate 200 Distilled spirits 332 Cobalt 246 DNA 354,358,362 Coenzyme A 84 DNA photolyase 70 Coenzyme models 50 et seq. DNA probes 368 Coenzyme recycling 100 et seq., 347 DNA, recombinant, in biosynthetic Computer graphics 198,221 studies 299 Computer programs 366 Dopamine l3-hydroxylase 172 Condensation reactions Drug development 172 thiazolium ion mediated 75 Drug toxicity 201 thiol esters in 86 Drug transport 180 Conformation, changes in 15 Copper containing proteins 240 Effective molarity 25,36 Copper in biological systems 238 et seq. Elastase Corrin 247 human leucocyte, inhibitors of 207 Corynebacterium spp. oxidase 108 et seq. 378 Index

Elastase---cont. Farnesyl pyrophosphate synthetase 284 porcine pancreatic, X-ray analysis Fatty acids, biosynthesis of 277 212 Ferredoxin 237 Elastin 208 Ferritin 233 Electrochemical recycling of N AD H Fischer, Emil 2 103 Flavin coenzymes Electron spin resonance, EPR 261 models 64 et seq. Electron transfer reactions 57 models, as photosensitizers 69 Elimination reaction, pectin lyase 324 models, asymmetric oxidation by 70 Emphysema, pulmonary 207 models, for oxygenascs 71 Emulsin 2 models, oxidation by 66 Enalapril 192 Flavin mononucleotide (FMN) in NAD Enantiomers 21 recycling 101 and biological activity 97 Flavins Enantioselective reduction 60, 108, 143 5-deaza 63 Endocytosis 366 in chemicaIly modified enzymes 151 Energy diagram 10, 272 Flavour components of cheeses 347 Enolase 356 Fluoroketones, in enzyme inhibitors Entropy, and enzymic catalysis 22 196,210 Enzyme catalysis, specificity 15 Folic acid 171 Enzyme models 50 et seq. Food industry 315 et seq rate enhancements in 42 Formate dehydrogenase 103 Enzyme stereoselectivity 114 Functional group modification in Enzymes and conventional reagents in synthesis by enzymes 128 et seq. competition 113 et seq. Enzymes GABA receptor 367,369 immobilized 104, 154 Gene cloning in animal feeds 356 in biosynthetic studies 281,283,291 in cheesemaking 338 et seq. in biosynthesis 268 in organic solvents 106, 117, 153 Genes for et seq. a-amylases 313 in synthesis 4,95 et seq. amylases 316 in industrial synthesis 105 ceIlobiohydrolases 328 in synthesis 4 ceIlulases 329 stability of 104 glucose oxidase 318 Enzymic catalysis lipoproteins 367 and association 24 Genes, structure 359 and entropy 22 Genetic disorder 365 Enzymic efficiency 31 Genetic engineering 6,98, 108, 156 Epoxidation by cytochrome P-450 Genetic relationships 359 model 149 Glucoamylases 315 Epoxides, chiral 123 mechanism of 316 Erwinia herbicola reductase 108 Glucose 6-phosphate dehydrogenase Erythromycin 278 101 Esterases in synthesis 117 Glucose isomerase 318,358 Esters, synthesis with enzymes in Glucose oxidase 319 organic solvents 153 Glucose syrups, production of 315 Evolution 31,358,363 Glutathione 84, 244 divergent 187 Glyceraldehyde 3-phosphate EXAFS 249,257 dehydrogenase 54 Exons 359 Glycine receptor 369 Index 379

Glyoxalase I 87 Insulin receptor 369 Gold 253 Integral membrane proteins 367 Grandisol, synthesis 117 Intermediates in reactions 11 Intermediates Haemocyanin 241 chiral, preparation of 116 et seq. Haemoerythrin 237 radical 138,160 Haemoglobin 234 reactive 12 chemically modified 151 tetrahedral 163 EPR spectrum 261 IntramolecuJar catalysis 34 Raman spectrum 260 Intramolecular effects 55 Haemoproteins 67 Intramolecular reactions 25 Haemosiderin 234 Introns 359 Hammond postulate 10 Invertase 321 Hydroxysteroid dehydrogenase 113 Invertin 2 Helix-turn-helix motif in protein Iron in biological systems 232 et seq. structure 361 Iron sulphur proteins 67 Hemicelluloses 321 Isopenicillin N synthetase 160,269 Hexokinase 102 mechanism of 274 Histones 362 Isoprene rule 284 Homology 357, 358 Isosteres for pep tides 195 Host-guest interactions 58 Isotope effects, in biosynthetic studies Human diet 318 271 Hybridization of oligonucleotides 369 Isotopic labels, chiral 114 Hydrogen bonding Isotopically labelled compounds, in catalysis by enzymes 366 stereoselective synthesis 103 in protein structure 361 Hydrogenase 102 Kinetics in investigating mechanism 12 Hydrolases 116 HydroxymethylglutaryIcoenzyme A f3-lactam antibiotics 180 et seq., 215 reductase 203 biosynthesis 269 Hydroxymethylbilane 267 stereochemistry of biosynthesis of 114 Hypercholesterolaemia 203 synthesis using enzymes 159 f3-lactamases 181, 185 et seq. Immobilization,ofNAD 103 f3-lactams, synthesis 119 Immobilized cells 114 Lactate dehydrogenase 100, 360 Immobilized enzymes 103, 104, 154 model for 54 in amino acid manufacture 120 LDL receptor 369 in food industry 318,321 Lead 252 Industrial enzymes 332 Leucotrienes, synthesis of 113, 118 Industrial oxidation, enzymes in 151 Leucovorin 133 Industrial production of L-aminoacids Linear free energy relationships 29 117 Lipases Industrial synthesis of aspartic acid 114 in cheese manufacture 340 Industrial use of enzymes in synthesis in organic solvents 153 105 non-natural substrates 154 Inhibitor binding, to dihydrofolate Lipcortin 371 reductase 177 Lipoic acid 84 molecular basis for selectivity 178 Lipoprotein 353 Inhibitors, bi-product 191 Lipoproteins 363 et seq. Insect attractants, synthesis 118, 119 Lipoproteins, plasma 203 Insulin 244 Lithium 256 380 Index

Lock and key hypothesis 3,219 Molybdenum complexes, in synthesis Lovastatin (mevinolin) 205 140 Low density lipoprotein 364 Monellin 360 Low density lipoprotein receptor, gene Monensin 377 203 Monobactam 181 Luciferase, models for 73 Monoclonal antibodies 362 Lysozyme 331 More O'Ferral-lencks diagram 10 Mucor rammanianus reductase 128 Macmlides, biosynthesis of 281 Multiple binding 40 Magnesium 250 Mutations, conservative 355 Maize 334 Myocrisin 253 Malting 332 Myoglobin 360 Maltose syrups 314 Manganese 246 Mechanism Na-KATPase 243 description of 9 Natural products, screening of 203 of enzymic catalysis 8 et seq. Newenzymes 158 and stereochemistry 20 Nicotinamide coenzyme binding, in Membrane proteins 366 dihydrofolate reductase 176 Membrane reactor 103 Nicotinamide coenzyme recycling 133 Memoryeffects 83 Nicotinamide coenzymes 21,40 Metal complexes, stability of 231 Nicotinamide coenzymes, models 51 Metal ions as drugs 253 et seq. as electron donors 57 biological function 228 asymmetric reduction by 60 catalysis by 52 host-guest 58 classification of 230 metal ion catalysis in 52 coordination geometries 231 non-covalent interactions in 56 Metallothinein 238, 251 oxidation by 61 Methotrexate 174 proton catalysis in 54 Methoxatin 68 Nicotinamide coenzymes, recycling 100 Methyl transferases 281 Nicotinamide nucleoside analogues, Methysalicylate synthase 278 synthesis 119 Mevastatin 203 Nitration, of phenol, biomimetic 148 Mexiprostil 132 Nitrogenase 248 Micelles 57,67,76,78,82, 136, 145 NMR 238,257,286 et seq. in studies of enzyme inhibition 212, casein 339 220 functionalized 147 in biosynthetic studies 265 et seq., Michael addition, asymmetric 143 296,299 Microorganisms in synthesis 128 Non-covalent interactions in catalysis 56 reactivity patterns 106 Non-enzymic proteins 353 Microscopic reversibility 13 Novel catalysts 362 Milk products 319 Milk proteins 339 Operator 366 Model reactions 34 Organometallic complexes in Molecular biology 221,354 stereoselective synthesis 126 advances in 156 et seq. Osteoarthritis 207 Molecular dynamics 220 Oxidation Molecularmodels 198,221 biomimetic 149 Molybdenum 67,239,248 by nicotinamide coenzyme models 61 Index 381

Oxygenases, flavin-dependent, models Pig pancreatic lipase (PPL) 117 for 71 in chiral epoxide synthesis 125 Pinitol, synthesis 159 Papain, chemically modified 151 Plant cell wall breakdown by enzymes Partition function 23 321 et seq. Pasteur 1 Plasmids 182,361 Pectate lyase 325 Plastocyanin 241 Pectin 322 Polyether antibiotics 277 Pectin esterase 326 Polyethers, biosynthesis of 279 Pectin lyase 324 Polygalacturonase 326 Pectinases 323 Polyketides, biosynthesis of 277 et seq. Penicillin binding proteins 182 Polymer supported cyclodextrin 141 Penicillin G 181 Polymer supported reactions 76 Penicillin V 185 Polymeric reagents 83 Penicillin, biosynthesis of 269 Polyphenylene 158 Penicillins, synthesis 159 Porphyrin ligand 228 Pentalenene synthetase 298 Porphyrins 5 Pentalenolactone, biosynthesis of 293 biosynthesis of 267 Pepsin 34 Potassium 250 in cheese manufacture 343 Prephenic acid 163 Pepstatin 195 Probes, DNA 368 Peptidases Prochirality 21 in synthesis 117 Proguanil 174 stereoselectivity in organic solvents Proline racemase 38 153 Prostaglandin E analogue, synthesis 130 stereoselectivity in organic solvents Prostaglandins, synthesis of 113, 119, 154 128 Peptide isosteres 195 Protease inhibitors, endogenous 207 Peptides et seq. cyclic 199 Protease N 155 synthesis with enzymes in organic Proteases solvents 153 acid 193 Phenoxypropanoate herbicides 96 in cheese manufacture 342 Pheromones, synthesis 118,119 metallo 190 Phosphofructokinase, site directed serine 187,207 mutagenesis of 366 Protecting groups 125 Phosphonates Protein chemistry, advances in 156 as enzyme inhibitors 192 et seq. as tetrahedral intermediate analogues Protein folding 357 162 Protein structure 358 et seq. Phosphonothricin 275 Proteins, interactions with DNA 360 Photochemical chlorination, of steroids Proton transfer 26,29,54 138 in inhibitor binding 177 Photochemical reactions 57,69,85 Pseudomonas putida, benzene Photolyase, DNA 70 dioxygenase 158 Photo sensitizers 69 Pullulanase 317 Physical methods in bioinorganic Pyridoxal 242 chemistry 257 Pyridoxal model, biomimetic synthesis Physical organic chemistry 8,22 142 Pig liver esterase (PLE) 117,131 Pyridoxal phosphate 80 et seq. 382 Index

Pyrimethamine 174 Sharpless epoxidation 123, 131 Pyrimidine based drugs 173 Sialic acids 126 Pyrroloquinoline quinone (POO) 68 Site directed mutagenesis 30, 32, 221, Pyruvate decarboxylase 20,39,41,77 268,274,354,371 inactivation 78 Snake venoms 190 Pyruvate dehydrogenase 38 Sodium 250 Sodium pump 243 Ouantum mechanical calculations 222 Solubility of substrates 131 Species specificity 176 Raman spectroscopy 237, 258 Starch Rate determining step 13,31 hydrolysis 319 Rational drug design 176 liquefaction of 333 Reaction intermediate analogue 40 processing of 308 Reaction profile, for penicillin saccharification of 333 biosynthesis 272 structure of 309 Receptors 353,367 et seq. Statistical mechanics 22 Receptors Steady state 12 as targets for drug design 171 Stellacyanin 241 cell surface 367 Stereochemical studies, in biosynthesis models for 145 272,285,287,294 structure determination of 368 Stereochemistry Red cells and enzymic specificity 15 EPR of 261 and reaction mechanism 20 NMRof 258 Stereoelectronic effect 15 Regulation of DNA expression 362 Stereogenic elements in molecules 21 Renin 189,193 Stereoselective synthesis Renin-angiotensin system, inhibitors of of isotopically labelled compounds 189 et seq. 103 Rennet 340 organometallic complexes in 126 Rennet, microbial 343 Stereoselectivity 2, 96 Reporter substrates 36 Steroids, selective functionalization of Repressor 360 138 Reverse transcriptase 249 Storage, of iron 233 Rhodium complexes, enantioselective Structure-activity relationship 214 reductions with 128 Substitution reactions 11, 57 Ripening, of fruit and vegetables 33 Substrate binding, in organic solvents RNA 248 153 as a catalyst 363 Subtilisin, chemically modified 151 editing 360 Sulphanilamide 171 Robinson, Sir Robert 5 Sulphonamides 214 Ruthenium porphyrin complex, Superoxide dismutase 240, 246, 248 biomimetic oxidation by 149 Supramolecular catalysis 44, 136 Synthesis, asymmetric 3 Second messenger 250,369 Synthesis, enzymes in 95 et seq. Selectivity Synthesis, selectivity in 95 et seq. covalent control of 138 in synthesis 95 et seq. Sequence homology in celluJases 329 Target enzyme, choice of 216 Serine proteases 187,208 Tentacle molecules 146 Sesquiterpene antibiotics 293 Terpenes, cyclic, biosynthesis of 284 biosynthesis of 286 Terpenoid cyclases 284 Index 383

Tetrahedral adducts, in serine protease Trimethoprim 174 inhibition 210 Triose phosphate isomerase 32,358 Tetrahydrofolic acid 131 Triparanol 201 Thalidomide 96 Troponin C 250 Thaumatin 360 Trp repressor 361 Thermoanaerobium brockii alcohol Trypsin dehydrogenase 112 in cheese manufacture 343 Thermodynamics 22 site directed mutagenesis of 355 Thermophilic organisms 105, 112,327 Tylactone synthase 281 Thiamine diphosphate 20,41 Tylosin 281 Thiamine pyrophosphate (diphosphate, Tyrosine hydroxylase 172 TPP), models for 75 Tyrosine kinase 369 Thiazolium ions 68 Tyrosyl t-RNA synthetase 30,356 in condensation reactions 75 Thiazolium salts 75 et seq. Uptake Thiazolium salts and f1avins 79 of copper 239 Thiazolium salts of iron 232 in asymmetric synthesis 77 in decarboxylation 77 Vanadium 243 Thienamycin 181, 186 Vanadium complexes, in synthesis 140 Thiol coenzymes 84 Vector 355 Thiol esters 86 Viscosity 33 Thiolligands 239,253,260 Vitamin BI 75 Thymidylate synthetase 173 Vitamin B6 80 Tocopherol 107 Vitamin BI2 247 Toxic metals 227,251 Vitamin C 108 Toxicity 201 Vitamin K synthesis, biomimetic 142 and metabolism 234 Trace element deficiency 228 X-ray crystallography 219,330,357 Transamination, pyridoxal mediated 81 of acid proteases 194 Transferrin 233 of bacterial carboxypeptidase• Transglucosidases 316 transpeptidase 187 Transition state of dihydrofolate reductase 176 binding 357 of porcine pancreatic elastase 212 stabilization 37 Xanthine oxidase 67, 249 Transition state analogue Xylose isomerase 324 and catalytic antibodies 162 W.r.t. penicillin action 181 Yeast 2 Transition state analogues 36 alcohol dehydrogenase, genetic for acid proteases 195 engineering of 157 Transition state and monoclonal condensation reactions mediated by antibodies 362 106 Transketolase, inactivation 78 dehydrogenases 117 Transpeptidases genes for amylases 316 bacterial 181 reductases 106 mechanism of action 183 Transport Zeolites 152 in biosynthesis 267 Zinc 248 offolates 180 Zinc proteases 190 Trichodiene synthetase 291