High Throughput Screening: The Discovery of Bioactive Substances

Front Cover
CRC Press, 1997 M05 6 - 704 pages
Furnishing the latest interdisciplinary information on the most important and frequently the only investigational system available for discovery programs that address the effects of small molecules on newly discovered enzyme and receptor targets emanating from molecular biology, this timely resource facilitates the transition from classical to high throughput screening (HTS) systems and provides a solid foundation for the implementation and development of HTS in bio-based industries and associated academic environments.

From inside the book

What people are saying - Write a review

We haven't found any reviews in the usual places.

Contents

CHEMICAL DIVERSITY AND GENETIC EQUITY SYNTHETIC AND NATURALLY DERIVED COMPOUNDS
3
DIVERSITY IS THE KEY
4
3 COMMERCIAL COMPOUND PURCHASES
5
4 NATURAL PRODUCTS
7
RICH RESOURCE OR CURIOSITY?
13
7 CONCLUSIONS
16
TEST SUBSTANCE SOURCES
17
CONVENTION ON BIOLOGICAL DIVERSITY1992
22
HOMOGENEOUS TIMERESOLVED FLUORESCENCE METHOD FOR DRUG DISCOVERY
345
2 THE THEORY OF HTRF
346
3 APPLICATIONS OF HTRF
349
4 INSTRUMENTATION AND ROBOTICS
358
TIMERESOLVED FLUOROMETRY ADVANTAGES AND POTENIALS
361
2 FLUOROMETRY
362
3 LANTHANIDES AS FLUORESCENT PROBES
367
4 TIMERESOLVED FLUOROMETRY IN BIOMEDICAL RESEARCH
372

CLINTON ADMINISTRATION PROPOSED INTERPRETATION
43
INTERNET ACCESS TO NATURAL PRODUCT INFORMATION
48
MICROCOLLECTION OF PLANTS FOR BIOCHEMICAL PROFILING
49
2 BOTANICAL AND CHEMICAL DIVERSITY
51
3 COLLECTION SCOPE
53
4 VOUCHER SAMPLING STORAGE AND RETRIEVAL
54
5 MICROCOLLECTION TECHNIQUES
56
6 DATA MANAGEMENT AND SAMPLE PREPARATION
61
7 EXTRACTION PROCESSES
63
8 REMOVAL OF INTERFERING SUBSTANCES
64
9 TEST SAMPLE PREPARATIONS IN MICROPLATE FORMAT
68
10 FOLLOWUP AND RECOLLECTION
69
11 CHEMOTAXONOMY AND PHYTOCHEMICAL TRACKING
72
12 CONCLUSIONS
75
ENZYMES AND MICROBES AS A SOURCE OF CHEMICAL DIVERSITY
77
2 THE PRODUCTION OF CHEMICALS BY MICROBIAL FERMENTATION
80
3 PRODUCTION OF CHEMICALS BY IMMOBILIZED MICROORGANISMS
85
4 FOREIGN PROTEIN SYNTHESIS BY MICROORGANISMS
90
5 STEROID TRANSFORMATIONS BY MICROORGANISMS
92
7 THE FUTURE
95
THE MARINE ENVIRONMENT AS A DISCOVERY RESOURCE
99
2 SCOPE AND DIVERSITY
103
3 ACCESS TO MARINE NATURAL PRODUCTS LIBRARIES
114
4 ECONOMIC CONCERNS
116
5 REQUIREMENTS OF AN EFFECTIVE ACQUISITION PROGRAM
118
6 ECOLOGICAL CONCERNS
125
7 SCALEUP DEVELOPMENT ALTERNATIVES
127
8 CONCLUSIONS
133
COMPOUND SOURCING CHEMICALLY GENERATED SCREENING LIBRARIES
145
INTRODUCTION
147
2 SOLID PHASE ORGANIC CHEMISTRY
148
4 PARALLEL SYNTHESIS OF INDIVIDUAL COMPOUNDS
150
5 AUTOMATION
153
RAPIDLY EXPANDING MOLECULAR DIVERSITY LIBRARIES FROM LIBRARIES
155
2 LIBRARY PREPARATION
156
3 DECONVOLUTION METHODS FOR NONSUPPORTBOUND COMBINATORIAL LIBRARIES
157
4 SOLUBLE COMBINATORIAL LIBRARIES
158
5 CONCLUSION
164
SYNTHESIS OF ENCODED SMALL MOLECULE COMBINATORIAL LIBRARIES VIA ECLiPS
167
2 ECLiPS TECHNOLOGY
172
3 ENCODED SMALL MOLECULE COMBINATORIAL LIBRARIES
175
4 CONCLUSION
188
PARALLEL ORGANIC SYNTHESIS USING PARKDAVIS DIVERSOMER METHOD
191
2 ORGANIC SYNTHESIS ON SOLIDSUPPORT
192
3 THE DIVERSOMER APPARATUS
194
4 ROBOTIC INTERFACING
195
5 EXAMPLES OF DIVERSOMER SYNTHESES
196
6 INFORMATION MANAGEMENT
204
RAPID DISCOVERY AND OPTIMIZATION OF BIOLOGICALLY ACTIVE SMALL MOLECULES USING AUTOMATED SYNTHESIS METHODS
209
3 ONTOGEN COMPOUND LIBRARIES
214
4 CONCLUSION
219
CMT A SOLUTION PHASE COMBINATORIAL CHEMISTRY APPROACH SYNTHESIS AND YIELD PREDICTION OF PHENAZINES
223
CONCEPT AND PHILOSOPHY
224
3 EXPERIMENTAL
231
4 DISCUSSION
240
DESIGN OF A DIVERSE SCREENING LIBARY
243
2 MATRIX CHEMISTRY
244
3 DIVERSITY OBJECTIVES
245
4 DESIGN PARAMETERS
247
5 EXAMPLE OF DESIGNED DIVERSITY
249
6 SUMMARY
250
AUTOMATING COMBINATORIAL CHEMISTRY CHALLENGES AND PITFALLS
251
COMBICHEM HIGH THROUGHPUT SCREENING FOR LEADS OPTIMIZATION
263
2 SAMPLE SCREENING RESULTS
264
3 CONCLUSIONS
269
4 SUMMARY
270
ASSAY TECHNOLOGIES AND DETECTION METHODS
273
INTRODUCTION
275
1 USING MORE EFFICIENT ASSAY METHODS TO REDUCE COMPROMISES IN SCREENING
276
2 THE DIVERSITY OF HTS METHODS
278
BIOASSAY DESIGN AND IMPLEMTATION
279
2 TARGET SELECTION
280
3 TYPES AND CHARACTERISTICS OF SCREENING ASSAYS
285
4 DECISION MAKING
302
SCINTILLATION PROXIMITY ASSAYS
307
2 AUTOMATABILITY OF SPA SCREENING ASSAYS
308
3 ASSAY THROUGHPUT USING SPA
310
4 NUMBER OF HITS IN SPA HTS ASSAYS
311
6 SIGNAL TO NOISE RATIOS UTILIZED IN SPA HTS ASSAYS
313
8 TYPES OF COMPOUND LIBRARIES TESTED WITH SPA
314
10 TYPES OF SCINTILLATION COUNTER USED WITH SPA
315
FLASHPLATE TECHNOLOGY
317
2 RECEPTOR BINDING ASSAYS ON FLASHPLATE
319
3 LIVE CELL ASSAYS ON FLASHPLATE
320
4 ENZYME ASSAYS ON FLASHPLATE
321
5 RADIOIMMUNOASSAYS ON FLASHPLATE
326
6 SUMMARY
327
ASSAYS FOR SMALL MOLECULE AGONISTS AND ANTAGONISTS OF THE NEUROTROPHIN RECEPTORS
329
2 RECEPTOR BINDING ASSAY
331
3 RECEPTOR ACTIVATION ASSAY
334
4 ASSAY AUTOMATION
341
5 AUTOMATION
373
ADAPTATION OF TIMERESOLVED FLUORESCENCE TO HOMOGENEOUS SCREENING FORMAT
377
2 MATERIALS AND METHODS
378
3 RESULTS AND DISCUSSION
381
4 SUMMARY OF ADVANTAGES
387
FLUORESCENCE POLARIZATION
389
2 THE POTENTIAL OF FLUORESCENCE POLARIZATION
390
4 INSTRUMENTATION
392
6 ASSAY CHARACTERISTICS
394
8 CHALLENGES IN HIGH THROUGHPUT SCREENING BY FP
396
REPORTER GENE ASSAY APPLICATIONS
401
2 REPORTER GENES AND THEIR PRODUCTS
402
3 DETECTION TECHNIQUES AND THEIR IMPROVEMENT
405
4 FUTURE ASPECTS
406
DEVELOPMENT OF A GENE EXPRESSIONBASED SCREEN USING QUANTITATIVE POLYMERASE CHAIN REACTION
413
3 DEVELOPMENT OF A GENE EXPRESSIONBASED SCREEN GEBS
415
4 THROUGHPUT OF GEBS
422
HIGHPERFORMANCE MICROPHYSIOMETRY IN DRUG DISCOVERY
427
2 SUMMARY OF MICROPHYSIOMETRY
428
3 BIOLOGICAL ISSUES
429
4 HIGHPERFORMANCE MICROPHYSIOMETRY
433
5 FUTURE EXTENSIONS OF MICROPHYSIOMETRY
439
6 CONCLUSION
440
BIOanalytical APPLICATIONS OF BIAcore an OPTICAL BIOSENSOR
443
2 SYSTEM DESIGN
444
3 APPLICATIONS
446
4 CONCLUSIONS
452
AUTOMATION AND ROBOTICS
455
Introduction
457
2 THE FUTURE OF AUTOMATION AND ROBOTICS
458
MANAGEMENT AND SERVICE ISSUES OF A CENTRALIZED ROBOTIC HTS CORE
461
2 SENIOR MANAGEMENT PERCEPTIONS AND EXPECTATIONS
462
3 BALANCING NEW TECHNOLOGY DEVELOPMENT AND DATA PRODUCTION
464
4 COPING WITH THE MONOTONY OF SCREENING
466
5 WORKING WITH SCIENTIST CUSTOMERS
467
6 SUMMARY
468
FLEXIBLE USE OF PEOPLE AND MACHINES
471
2 APPROACHES TO AUTOMATION IN HTS
472
4 IMPLEMENTING AN AUTOMATION PROJECT
477
5 FUTURE PROSPECTS FOR AUTOMATION IN HTS
480
BARCODE TECHNOLOGY AND A CENTRALIZED DATABASE KEY COMPONENTS IN A RADIOLIGAND BINDING PROGRAM
483
2 METHODS
484
3 DISCUSSION
490
4 GLOSSARY OF TERMS
491
FACTORS FOR THE SUCCESSFUL INTEGRATION OF ASSAYS EQUIPMENT ROBOTICS AND SOFTWARE
493
2 DEFINING THE SCREENING OBJECTIVES
494
4 HARDWARE
497
5 COMPUTING
500
6 FURTHER DEVELOPMENT OF THE HTS FACILITY
504
ACCELERATING THE DISCOVERY PROCESS WITH AUTOMATION AND ROBOTICS A SURE BET OR A RISKY VENTURE?
509
2 BACKGROUND
510
3 CRITICAL SUCCESS FACTORS
512
4 EXAMPLES
522
5 CONCLUSIONS
523
PERSPECTIVES ON SCHEDULING
525
2 SCHEDULING
526
3 COMMUNICATION TOOLS
535
4 USER INTERFACE
539
5 CONCLUSION
544
DATA RETRIEVAL HANDLING AND INTEGRATION
547
Introduction
549
DATABASE SYSTEMS
551
3 CLIENTSERVER SYSTEMS
564
4 PERFORMANCE AND DESIGN CONSIDERATIONS
571
5 CHEMICAL STRUCTURE DATABASES
579
6 PROGRAMMING CONSIDERATIONS
580
7 FINAL SUMMARY POINTS
581
SYSTEMS INTEGRATION
583
2 HTS DATA MANAGEMENT
584
3 CONCLUSION
596
DATA MANAGEMENT AND TRACKING FOR NATURAL PRODUCT PROGRAMS
599
2 USER REQUIREMENTS
603
3 IMPLEMENTING AN EFFECTIVE SYSTEM
612
4 CONCLUSIONS
619
LABORATORY DESIGN AND MANAGEMENT
623
INTRODUCTION
625
PLANNING AND IMPLEMENTING AN HTS PROGRAM
627
3 PROGRAM LOGISTICS
632
4 ASSAYS
635
5 SAMPLES
639
6 RESOURCING
644
7 MANAGEMENT CONSIDERATIONS
651
ESTABLISHING AND HTS PROGRAM INA STARTUP BIOTECHNOLOGY COMPANY
653
2 PLANNING THE SCREENING PROGRAM
655
3 SAMPLES FOR SCREENING
656
4 EQUIPPING THE HTS LABORATORY
658
5 DEVELOPING HIGH THROUGHPUT SCREENS
660
6 REAGENT SUPPLY
661
8 LEAD DISCOVERY
666
INDEX
669
Copyright

Other editions - View all

Common terms and phrases

Bibliographic information