Combinatorial Chemistry & High
Throughput Screening, Vol. 7, No. 6, 2004
Contents
Microarray-Based
Technologies and Beyond
Guest Editors: Shao Q. Yao /
Sridar V. Chittur
DNA
Microarrays: Tools for the 21st Century Pp.531-537
Development
of Functional Protein Microarrays for Drug Discovery: Progress and Challenges Pp.539-546
Fang
X. Zhou, Jaclyn Bonin and Paul F. Predki
Recent
Advances in Peptide-Based Microarray Technologies Pp.547-556
Resmi
C. Panicker, Xuan Huang and Shao Q. Yao
Recent
Advances in Small Molecule Microarrays: Applications and Technology Pp.557-564
D.P.
Walsh and Y.T. Chang
Carbohydrate
Arrays for Functional Studies of Carbohydrates Pp.565-574
Injae
Shin, Jin Won Cho and Doo Wan Boo
Perspectives
in Tissue Microarrays Pp.575-100%
Till
Braunschweig, Joon-Yong Chung and Stephen M. Hewitt
High
Throughput Determination of Gains and Losses of Genetic Material Using High Resolution
BAC Arrays and Comparative Genomic Hybridization Pp.587-596
John
K. Cowell
Chemical
Approaches for Live Cell Bioimaging Pp.597-604
Rajavel
Srinivasan, Shao Q. Yao and Dawn S.Y. Yeo
Abstracts
[Back to top] DNA
Microarrays: Tools for the 21st Century
Sridar
V. Chittur
Profiling of gene expression patterns with microarray technology is widely used in both basic and applied research. DNA microarrays have also shown great promise in clinical medicine and are paving the way toward effective pharmaceutical drug discovery and individualized drug regimens. With growing utilization of this high-throughput technology, new applications are making headlines on a regular basis. This review aims to outline the pros and cons of this methodology and direct the reader towards available useful resources. Various major array formats such as high-density oligonucleotide arrays and spotted cDNA arrays are examined, and advantages and options for using each format are presented. Factors important for the design
and analysis of microarray experiments are also discussed.
[Back to top] Development of Functional Protein
Microarrays for Drug Discovery: Progress and Challenges
Fang
X. Zhou, Jaclyn Bonin and Paul F. Predki
Functional protein microarrays promise new approaches to address longstanding challenges in drug discovery and development, with applications ranging from target identification to clinical trial design. However, their widespread adoption will be contingent upon a robust ability to develop and manufacture arrays in support of these applications. This review will address the major areas of relevance to the development of functional protein microarrays; protein content, surface chemistry, manufacture and assay development. Successful development will empower multiple drug research applications, help fill future HTS pipelines and guide next generation combinatorial chemistry efforts.
[Back to top] Recent
Advances in Peptide-Based Microarray Technologies
Resmi
C. Panicker, Xuan Huang and Shao Q. Yao
Peptide array is a rapidly growing tool that provides both large-scale and high-throughput capabilities for protein detection and activity studies. Materials presented in this review will examine the recent advances in the field of peptide microarray with special emphasis on the generation and applications of high-density arrays of peptides on glass slides.
[Back to top] Recent Advances in Small Molecule Microarrays: Applications and
Technology
D.P.
Walsh and Y.T. Chang
The field of Small Molecule Microarray’s (SMM’s) is an ever-expanding part of the larger microarray field. SMM’s are array based detection systems that use small molecules as probes immobilized on a variety of microarray surfaces that are screened against a number of targets for purposes including, but not limited to, protein-small molecule ligand recognition and protein function profiling. This review covers the recent advances in the field with particular emphasis on the successful applications of SMM’s, as well as technical advances in platform optimization and novel small molecule immobilization strategies.
[Back to top] Carbohydrate Arrays for Functional Studies of Carbohydrates
Injae
Shin, Jin Won Cho and Doo Wan Boo
Carbohydrates, as components of glycoproteins, glycolipids and proteoglycans, play an important biological role as recognition markers through carbohydrate-protein interactions. For the most part, biophysical and biochemical methods have been used to analyze these biomolecular interactions. In contrast, less attention has been given to the development of high-throughput procedures to elucidate carbohydrateprotein recognition events. Recently, carbohydrate arrays were developed and employed as a novel highthroughput analytic tool for monitoring carbohydrate-protein interactions. This technique has been used to profile protein binding and enzymatic activity. The results have shown that carbohydrate binding to the corresponding lectins is highly selective and that the relative binding affinities are well correlated with those obtained from solution-based assays. In addition, this effort demonstrated that carbohydrate arrays could be also utilized to identify and characterize novel carbohydrate-binding proteins or carbohydrate-processing enzymes. Finally, the results of this investigation showed that lectin-carbohydrate binding affinities could be quantitatively assessed by determining IC50 values for soluble carbohydrates with the carbohydrate arrays. The results of these studies suggest that carbohydrate arrays have the potential of playing an important role in basic researches, the diagnoses of diseases and drug discovery.
[Back to top] Perspectives in Tissue Microarrays
Till
Braunschweig, Joon-Yong Chung and Stephen M. Hewitt
Tissue microarrays (TMAs) are means of combining tens to hundreds of specimens of tissue onto a single slide for analysis at one time. TMAs are most frequently constructed from paraffin embedded tissue; however, they can be constructed from frozen tissue. The construction of TMAs is flexible, meeting the focused needs of the investigator. A TMA slide can be processed like an ordinary tissue section, and used for histochemical, immunohistochemical staining or in situ hybridization. Combined with automated new image analysis systems, TMAs are a powerful molecular profiling tool. By confirming the findings of microarray experiments or protein arrays, TMAs can be applied systematically to global cellular network analysis within tissue cell. TMAs are commonly used to confirm the results of expression microarrays as well as in the development of diagnostic and prognostics markers for clinical applications. This review will cover recent advancements in technology for the construction and use of TMAs. Because TMAs can be constructed from archival paraffin embedded tissue, they open up the vast archive of patient samples and make them accessible for medical research. TMAs play an ever increasing role in translational medicine, bridging the chasm of discovery at the research bench to the demonstration of clinical utility prior to implementation in patient care.
[Back to top] High Throughput Determination of Gains and Losses of Genetic
Material Using High Resolution BAC Arrays and Comparative Genomic Hybridization
John
K. Cowell
Chromosome analysis has been a cornerstone both for the identification of genetic defects that predispose to a variety of genetic syndromes as well as for the analysis of cancer progression. The relatively low resolution of metaphase chromosomes, however, only allows characterization of major genetic events which are defined at the megabase level. The development of the human genome-wide bacterial artificial chromosome (BACs) libraries which were used as templates for the human genome project made it possible to design microarrays containing these BACs which can theoretically span the genome uninterrupted. Comparative genomic hybridization to these arrays using test and reference DNA samples reveals numerical chromosome abnormalities (deletions, gains and amplifications) which can be accurately defined with a resolution depending on the density of the arrays. Analysis of test DNA samples using these arrays reveals low level deletions and amplifications that cannot be detected by chromosome analysis and provides a global view of these genetic changes in a single overnight hybridization using a high throughput approach. The extent of the genetic changes can then be determined precisely and the gene content of the affected regions established. These BAC arrays have widespread application to the analysis of constitutional genetic abnormalities associated with human diseases as well as cancer patients and their tumors. The development of similar BAC arrays for the mouse genome means that it is now possible to extend the CGHa approach to the study of genetic disorders and cancer models in mice.
[Back to top]
Chemical Approaches for Live Cell Bioimaging
Rajavel
Srinivasan, Shao Q. Yao and Dawn S.Y. Yeo
We review various advancements in small molecule probes, intein-based labeling methods, and the incorporation of synthetic amino acids into proteins for live cell imaging experiments. Finally, recent developments in quantum dots-based labeling are briefly reviewed.