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Analitical techniques in combinatorial chemistry - Swarth M.E.

Swarth M.E. Analitical techniques in combinatorial chemistry - Marcel Dekker, 2000. - 311 p.
ISBN 0-8247-1939-5
Download (direct link): analyticaltechniquesincombinatorialchemistry2000.pdf
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Dihydroxy-benzoic acid (DHP),
35
Dimethylsulfoxide, 210 Drug discovery stages, 2 candidate selection, 4 late stage lead optimization, 3-4,
8
lead compound, 2 lead discovery, 2, 8 lead optimization, 3, 196
Edman degradation, 13 Enzyme modulated microanalysis (EMMA), 140 Enzymes kinase, 199
phosphotransferase, 198 proteases, 198 metallo, 210-211 serine, 210-211 Extraction
immunoaffinity LC/MS, 213 resins, ion exchange, 5 solid phase, 175 and cartridges, 22 and robots, 5
Filtration, 6, 7, 9 immunoaffinity ultra-, 45 and LC/MS, 215 pulsed ultra- and MS, 215 Fluorescein isothiocyanate (FITC), 151, 154
Fluorescein resonance energy transfer system, 199
Fourier transform infrared spectroscopy
accessories, Golden Gate, 68 accessories, Split Pea, 68 Fellgetts advantage, 65 Jacquinots advantage, 65 and microspectroscopy, 70 and Raman, 74 resin, structures bound, 7, 65
Gas chromatography
electron capture detection, 15
Hexapeptides, 12
HPLC (see Liquid chromatography)
Information management, 173-192, 207-208 Insulin, 151
Islets of Lagerhans, 151
Laser induced fluorescence (LIF), 153 Libraries
benzodiazepine, 45 binary encoded, 15 chemically encoded, 12-15, 17 acyl-tripeptide amide-, 15 polymers, bifunctionalized,
13
tags, haloaromatic, 15 tags, oligonucleotide, 13 tags, peptide, 15 tags, radiofrequency, 16 mechanically encoded, 15-17 orthogonal pools, 12 predicting MS of, 43 purification, 21
receptor-ligand interactions in,
51
screening
against receptors, 44 binding affinities, 43 virtual, 22
Index
299
Linker amide, 15 chemical, 7 ester, 7
functional group acetal, 7
carboxylic acid, 7 hydroxyl, 7 oxidatively labile, 15 photolabile, 15 Liquid chromatography, 113-136 affinity, 134, 213 automated multichannel, 125 capillary, 133
of chemically encoded libraries, 15 columns
immunoaffinity, 49 protein-G, 45
restricted access media, 213 reverse phase, 45, 114 detection
chemluminescence, 115, 126 127
evaporative light scattering, 22, 115, 125-127 photodiode array, 115 equilibration, 121 and fraction collection, 129 intelligent automated, 129 and generic methods, 114-122 gradient, 114 just in time, 121 and infrared spectroscopy, 71-73 and injection overhead, 118 and mass-directed autopurification, 113, 128-132 microbore, 121 microelectromechanical, 134 and MS, 30, 44, 213 and atmospheric pressure ionization, 117 and electrospray ionization, 117 and NMR, 97-99, 134 open access, 114, 127-128
[Liquid chromatography] parallel mode, 119
with rapid equilibration, 121-123 preparative, 5
and sample pooling, 122-124 sequential mode, 119 and splitters, 130 backstreaming, 131 and two column regeneration, 123 125, 129 Liquid handlers robotic, 5
Mass spectrometry, 29-64
atmospheric pressure chemical ionization, 30 bioaffinity characterization, 51, 214 capillary electrophoresis, 36, 44 affinity, 46-47 direct infusion, 30, 43 electrospray ionization, 30, 51, 212 flow injection analysis, 47 Fourier transform ion cyclotron, 34, 35, 39-42 and ionization efficiencies, 31 and isotopes, 30 mass filters
discreet, 31, 33, 34 matrix-assisted laser desorption ionization, 29, 35-39, 43,49,51, 180 252Cf plasma, 35 secondary ion, 35 time of flight, 35 nanoelectrospray, 30 and predicting, 43 probe affinity, 49-51 quadrapole ion traps, 30-31 and sequencing, 37 triple quad, 30-34 Micellar electrokinetic capillary
chromatography (MECC or MEKC), 140 Microheterogeneity, 145, 147 Morphine, 153
300
Index
Nuclear magnetic resonance (NMR) spectroscopy, 77-111 affinity, 103
automated data collection, 92 diffusion encoded, 102, 105 flow, 99 robotic sampling, 99 gel phase, 77-82 19F, 81 3IP, 82
and liquid chromatography, 97-99 magic angle spinning, 82-85 l3C, 83-85 l9F, 85 H, 82-83
and Merrifield and Wang resins, 85 3IP, 85
spin echo correlated, 89-91 and multipin crown resins, 93-96 pulsed field gradient, 102 and resin bound structure elucidation, 7
for screening libraries, 53 and structures, 29 using Tentagel beads, 88 and robotics, 92 and Wang resin, 89, 91 two-dimensional, 86-93 carbon-hydrogen correlated, 86 and gel phase, 86 and Heck reaction, 90 heteronuclear multiple quantum correlation, 87 nuclear Overhauser enhanced (NOESY), 88
Pentapeptides, 12 Phencyclidine, 153 Photolysis, 15
Robotics
integrated high-throughput screening, 201-202 liquid handling, 201
Sampling statistical, 11 Screening (high-throughput), 174-192, 194, 208-209 bioanalytical, 193-218 multiplexed high-throughput, 209-211
and robotics, 195 Secondary amines, 15 Software array information management (AIMS), 207 array production module (),
207
optical character recognition (OCR), 16
process control and monitoring (PCMS), 207 Spatially addressable combinatorial arrays, 203-205 design and automated synthesis,
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