Applying Genomic and Proteomic Microarray Technology in Drug Discovery

by Matson; Robert S.

• ISBN13: 9780849314698
• ISBN10: 0849314690
• Format: Hardcover
• Copyright: 2004-12-28
• Publisher: CRC Press

Summary

Microarrays play an increasingly significant role in drug discovery. Written by a leader in the field, Applying Genomic and Proteomic Microarray Technology in Drug Discovery highlights, describes, and evaluates current scientific research using microarray technology in genomic and proteomic applications. The author addresses the drawbacks, helping you avoid unnecessary pitfalls, and provides practical tips on how to employ the technology in drug discovery and development.The book details the commercial landscape, covering the many issues surrounding the future adoption of gene expression and protein microarrays for pharmacogenomic and pharmacoproteomic applications. The author critically assesses those studies that have helped define applications in genomics and proteomics, explains gene expression microarray applications, and examines the utility of the protein microarray. He covers alternative substrates and the preparation of various surface chemistries together with their suitability for immobilization of nucleic acids and proteins. He delineates the mechanics of microarraying including environmental conditions, printer and pin performance, as well as discussion regarding setting up the print run. The book supplies protocols for printing nucleic acids and proteins and an in-depth discussion of other important parameters such as print buffers (inks) and factors influencing print quality.An understanding of the making of a microarray is fundamentally important to those interested in producing "spotted" arrays and their proper use. As this technology expands in popularity and usefulness, industry experts must grasp the fundamental principles behind it, its strengths, and its limitations. A basic reference for users of microarray technology in drug discovery, this book offers a detailed perspective and insight into the present and future uses of this technology.

Table of Contents

Chapter 1 Quantitative biology: The "Omics" Era	1	(30)
Introduction	1	(1)
Microarray format	2	(3)
Terms and definitions	2	(3)
General utility	5	(2)
Biomedical testing	5	(1)
Biotechnology sector trends	6	(1)
The Omics Era	7	(4)
Role of gene expression microarrays in drug discovery	11	(3)
Toxicogenomic applications	14	(1)
Proteomics today: The great challenge	14	(1)
Potential role for protein microarrays in drug discovery	15	(2)
Critical issues with protein microarrays	17	(6)
Stability and performance	17	(2)
Content	19	(1)
Detection	19	(1)
Micro-ELISA formats	20	(1)
Protein profiling formats	21	(1)
Near-term biomedical applications	22	(28)
Cytokines	22	(1)
Autoimmune diseases and allergies	22	(1)
Future medicine: Pharmacoproteomics or pharmacogenomics?	23	(3)
References	26	(5)
Chapter 2 Commercial microarrays	31	(26)
Introduction	31	(1)
In situ arrays	31	(7)
Ex situ or spotted arrays	38	(6)
3D and 4D chips	44	(1)
Flow-through biochips	45	(1)
Electronic biochips	46	(4)
Future opportunities	50	(3)
DNA microarrays	50	(1)
Protein microarrays	51	(1)
Tissue and cell microarrays	52	(1)
References	53	(4)
Chapter 3 Supports and surface chemistries	57	(36)
Introduction	57	(1)
Substrates	57	(31)
Membrane substrates	59	(2)
Use with nucleic acids	59	(1)
Use with proteins	60	(1)
Glass substrates	61	(7)
Use with nucleic acids	61	(5)
Use with proteins	66	(2)
Plastic substrates	68	(3)
Use with nucleic acids	68	(2)
Use with proteins	70	(1)
Physical features	71	(2)
Hydrogels	71	(2)
Surface chemistries	73	(13)
Linkers	73	(10)
Reactive groups	83	(3)
Preparation of glass substrates for derivatization	86	(8)
Beattie et al. (1995): Attachment of oligonucleotides by epoxide	86	(1)
Beier and Hoheisel (1999): Attachment of dendrimer linkers from amine	86	(1)
Zammatteo et al. (2000): Preparation of carboxylic acid and aldehyde slides	86	(1)
Belosludtsev et al. (2001): Vacuum amine and epoxy silanization protocols	87	(1)
Benters et al. (2002): Preparation of carboxyl- and NHS-activated surfaces	87	(1)
Lee et al. (2002): Preparation of PEI-coated slides	88	(1)
Summary	88	(1)
References	89	(4)
Chapter 4 Arraying processes	93	(54)
Introduction	93	(1)
Creating spotted microarrays	94	(30)
Substrates	94	(1)
Probe composition (print buffer)	95	(1)
Printing environment	96	(1)
Printing mechanics	97	(21)
Microarray pins	104	(2)
Other approaches	106	(6)
Printer performance	112	(1)
Pin performance	113	(2)
Microarray design	115	(3)
Setting up a print run	118	(2)
Printing parameters	120	(2)
Preparing probe ink	122	(2)
Optimization of probe concentration	124	(1)
Protocols for printing nucleic acids	124	(14)
cDNA microarray	124	(1)
Oligonucleotides	125	(7)
Dimethyl sulfoxide	127	(1)
Betaine	127	(2)
Evaporation	129	(3)
Print quality assessment	132	(4)
Backgrounds	136	(2)
Protocols for printing proteins	138	(6)
Antibody arrays	139	(8)
Protocol of Haab et al. (2001)	139	(1)
Protocol of MacBeath and Schreiber (2000)	140	(4)
References	144	(3)
Chapter 5 Gene expression: Microarray-based applications	147	(42)
Introduction	147	(1)
Applications demonstrating DNA microarray utility	147	(12)
Gene expression	147	(12)
Biomedical research applications	159	(25)
Drug discovery	159	(2)
Drug toxicity	161	(3)
Cancer	164	(12)
Infectious disease	176	(4)
Other disease states	180	(16)
Hearing loss	181	(1)
Bone pathology	181	(1)
Glaucoma	182	(1)
Multiple sclerosis	182	(2)
References	184	(5)
Chapter 6 Protein microarray applications	189	(50)
Introduction	189	(1)
Spot theory	189	(7)
Applications demonstrating protein microarray utility	196	(13)
Microtiter-based antibody arrays	196	(2)
Membranes	198	(3)
Glass slides	201	(8)
Measuring microarray performance	209	(8)
Sensitivity and dynamic range	209	(8)
Other microarray formats useful for proteomic applications	217	(17)
mRNA-protein fusions	217	(2)
Protein in situ array (PISA)	219	(1)
Aptamers	220	(3)
Universal protein array	223	(6)
Peptide arrays for antibody detection	229	(1)
Phage display antibody selection	229	(1)
Protein kinase microarray	230	(1)
Second generation proteomics	231	(3)
References	234	(5)
Index	239