DeutschesFachbuch.de : Modified Nucleosides in Biochemistry, Biotechnology and Medicine

INHALTSVERZEICHNIS | öffnen

Contents
Preface XIX
List of Contributors XXI
Part I Biochemistry and Biophysics 1
1 Investigations on Fluorine-Labeled Ribonucleic Acids by 19 F NMR Spectroscopy 3
Christoph Kreutz and Ronald Micura
1.1 Introduction 3
1.1.1 NMR Spectroscopic Properties of the 19 F Nucleus 3
1.1.1.1 General NMR Spectroscopic Properties 3
1.1.1.2 19 F versus'H NMR Spectroscopy 3
1.1.1.3 Factors Affecting the 19 F Chemical Shift in Biomolecules 5
1.1.1.4 Fluorine Relaxation in Biological Systems 6
1.1.1.5 Solvent-Induced Isotope Shifts of 19 F NMR Resonances 7
1.1.2 19 F NMR Spectroscopy of Proteins 7
1.1.2.1 Incorporation of Fluorinated Amino Acids into Proteins 7
1.1.2.2 19 F NMR Spectroscopic Studies of Proteins 8
1.2 19 F NMR Spectroscopy of Nucleic Acids 13
1.2.1 Nucleic Acids with Fluorinated Nucleobases 14
1.2.1.1 Transfer RNAs 14
1.2.1.2 Hhal Methyltransferase in Complex with DNA Duplexes 14
1.2.1.3 Minimal Hammerhead Ribozyme 15
1.2.1.4 HIV TAR RNA 17
1.2.2 Nucleic Acids with Fluorinated Ribose Units 19
1.2.2.1 Rlinv RNA 29
1.2.2.2 RNA Secondary Structure Equilibria 21
1.2.2.3 RNA Ligand Binding 22
1.2.3 Influence of Fluorine Modifications on Nucleic Acid Structure 22
1.3 Conclusions 24
References 24
2 8-Oxo-7,8-Dihydro-2 -Deoxyguanosine: A Major DNA Oxidation Product 29
Jean Cadet and Paolo Di Mascio
2.1 Introduction 29
2.2 Formation of 8-Oxo-7,8-Dihydroguanine 30
2.2.1 Single Lesion 30
2.2.1.1 OH Radical 31
2.2.1.2 One-Electron Oxidation 31
2.2.1.3 Singlet Oxygen 32
2.2.2 Tandem Lesions 34
2.3 Reactivity of 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine 35
2.3.1 One-Electron Oxidation 35
2.3.1.1 Secondary Oxidation Products 36
2.3.1.2 DNA-Protein Crosslinks 37
2.3.2 Singlet Oxygen 37
2.3.2.1 Nucleoside 37
2.3.2.2 Oligonucleotide 38
2.4 Formation of 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine in Cellular DNA 39
2.4.1 Methods of Measurement 39
2.4.1.1 HPLC Methods (HPLC-ECD and HPLC-MS/MS) 39
2.4.1.2 Enzymic Assays 40
2.4.2 Indirect Effects of Ionizing Radiation (OH Radical) 41
2.4.3 High-Intensity UV Laser Irradiation (One-Electron Oxidation) 41
2.4.4 UVA Photosensitization ( C 0 2 ) 42
2.5 Synthesis of 8-Oxod-Guo and Insertion into Oligonucleotides 42
2.6 Conclusions 43
References 44
3 Modified DNA Bases: Probing Base-Pair Recognition by Polymerases 49
Eric T. Kool
3.1 Introduction 49
3.1.1 The Importance of Understanding DNA Polymerases 49
3.1.2 The Utility of Modified Nucleobases in Probing Mechanisms 50
3.1.3 The Scope of this Chapter 50
3.2 Basic Principles and Methods in Replication 51
3.2.1 The Chemistry of Polymerases 51
3.2.2 Different Classes of Polymerases 51
[weiter lesen]

REGISTER | öffnen

Index
Aab-initio calculations 57, 158, 166, 309
ab-initio molecular orbital (MO) 157
ACC synthase 234, 237
acetic acid 175
acetic anhydride 175, 404
acetonide-protected amino sugar 567
acquired immunodeficiency syndrome
- (AIDS) 426
activation enzymes 513
- uridine-cytidine kinase (UCK) 513
acute lymphoblastic leukemia (ALL) 452
acyclic analogues 576
acyladenylate intermediate 375
acyladenylate mimetics 374
- salicyl-AMS 374
acylated acyl carrier protein 227
acyl hydroxamoyl phosphate linker 378
acyl sulfamate linkage 367, 373
addition-elimination reaction 551
adduct formation 97
adefovir dipivoxil 603, 604
adenine heterocycles 385
adenosine kinase 525, 540
adenosine receptors 536
adenine nucleosides 317
- chiral resolution 317
adenosine agonists 434
adenosine analogue(s) 175, 416
adenosine deaminase (ADA) 311, 367
adenosine kinase activity 485
adenosine kinase inhibition 581
adenosine nucleoside 367
- metabolism 367
adenosine receptors 433, 444
- modulators 433
adenosine residues 17
adenosine scaffold 385
adenosine triphosphate (ATP) 223
adenylation domains/enzymes 371
adenylation enzymes 381
AsbC 381
- DhbE 381
AdoMet 224, 225, 227-231, 234, 236-238, 240
adenosyl group donor 228
aminocarboxypropyl group donor 227
analogues 231, 236
aziridine analogues 238
- biochemistry 224, 231
- biosynthesis 230 -chemistry 231
- metabolism 230
- methionine side chain 238
- nitrogen analogues 237
- pharmaceutical 240
- radical source 229
- riboswitch 236, 238
- ribosyl group donor 228
- ribosyl moiety 225
- selenium 234
- sulfone analogues 236
- sulfoxide 236
- tellurium analogues 234
AdoMet-dependent enzymes 232, 236, 241
AdoMet-dependent reactions 230, 231
AdoMet-dependent riboswitches 230
AdoMet-dependent transfer reactions 223
AdoMet-initiated radical chemistry 229
AdoMet synthetase(s) 231, 233, 234, 238
affinity chromatography 503
aglycone modifications 571
AHL 228
- metabolism of 228
AHL-mediated quorum sensing systems 227
AIDS see acquired immunodeficiency
- Syndrome alicyclic groups 456
O-alkyl hydroxylamine 255
alkylated thioadenosines 223
ALL see acute lymphoblastic leukemia N-alkylated nucleosides 311
allylic acetate 550
anti-tumor activities 592
allylic alcohol 328
- deoxygenation 328, 371, 375
aminoacyl tRNA synthetases 371, 375
aminoglycoside-based antibiotics 227
amino group donor 229
amino-substituted side chains 296
AMP deaminase 501
- fluorimetric assay 501
ampullariella regularis 525
anti-AIDS drugs 49
anti-apoptotic enzymatic signal 443
anticancer drug discovery program 635
anti-cancer drugs 587
anticancer nucleoside analogues 639
anti-Epstein-Barr virus (EBV) activity 578
anti-HCMV activity 411
anti-HIV agent 187
anti-parallel triplexes 294
anti-seizure mediator 437
antisense oligonucleotides 134
anti-tumor activities 592
antitumor agent 485
antiviral agents 601
adefovir 601
- tenofovir 601
apoptosis 641
apoptotic response 643
aqueous Solutions 348
aqueous trifluoroacetic acid (TFA) 366, 568
AR-induced vasodilation 439
aristeromycin 532
- modification 532
AR ligands 433
AR proteins 434
area under concentration curve (AUC) 590
arginine residues 226
aryl acid adenylation domains 374
aryl-capped siderophores 388
aryl ring 379
- importance of 379
aspase-dependent apoptosis 519
ataxia telangiectasia mutated (ATM) 519
ATP see adenosine triphosphate
ATP binding pocket 385
autoimmune disorders 452
- Crohn's disease 452
- psoriasis 452
autoimmune inflammatory disorders 433
aziridine cofactors 239
BBacillus anthracis 370, 381, 492
Bacillus subtilis 121
backbone-protein interactions 338
bacteriophage T 4 116
Baeyer-Villiger Oxidation 401
base analogues 64
base flipping enzyme 337, 338
base-modified analogues 478
base-pair extension 51
base-pair synthesis 51, 69
base-protected oligomers 164
Baylis-Hillman reaction 326
Benner Hydrogen-Bonding Variants 54
benzimidazole deoxynucleosides 56
- synthesis 56
benzimidazolium triflate 105
benzoate group 572
benzyl chloromethyl ether 465
bicyclic cylopentanons 418
bicyclic intermediate 416
biofilm formation 352
biological Systems 6 biomolecule's architecture 6 biotin synthase 229
bipolar depression 241
- anxiety 241
- hypomania 241
- mania 241
bisubstrate inhibitors 374
bone marrow cells 589
bovine rhodopsin 434
butylammonium hydrogen carbonate 346
CC-5-substituted pyrimidine nucleosides 251
- synthesis 252
Cambridge structural database 309
Cancer cells 587
- long-term frequent treatment 587
capecitabine 588, 593
- discovery 588
- efficacy 593
- therapy 594
carbene-mediated intramolecular
cyclopropanation 317
carbenoid intermediate 311
carbocyclic-oxetanocin-G (lobucavir) 399
carbocyclic amine 321
carbocyclic analogues 431, 573
carbocyclic nucleosides 309, 393, 403, 416, 526
- activity of 393
- biological activity 393
- mechanism 393
- processing 393
- synthesis 393, 416
carbocyclic oxctanocin analogues 404
carbocyclic oxetanocins 404
carbohydrate-modified nucleosides 636
carbohydrate Systems 76
carcinogens 97
cardiac arrhythmias 435
cardiac ischemia 433
cardiovascular System 437
carrrier domain 371
catalytic hydrogenation 458
catechol-O-MTase (COMT) 227
cell-cycle proteins 520
CEM cells 642
chemical shift anisotropy (CSA) 12
chemical shift values 4, 5
chemical synthesis 105
chemokines 440
chiral cyclopentenol 313
Chlamydia pneumoniae genotypes 148
- p-chlorobenzoate group 569
[weiter lesen]