Small molecule microarray

Key Words Peptide microarrays small-molecule microarrays small-molecule immobilization peptide immobilization chemoselective ligation. 

Figure 16.2 Fluorous small-molecule microarrays. Small-molecule histone deacetylase (FiDAC) binders are noncovalently immobilized onto a glass slide coated with fluorocarbon compounds. An antibody labeled with a fluorescent dye recognizes HDAC proteins. See color plate 16.2.

For example (a) Small-Molecule Microarrays Covalent Attachment and Screening of Alcohol-Containing Small Molecules on Glass Slides, P. ). Hergenr-OTHER, K. M. Depew, S. L. Schreiber,... 

J. Am. Chem. Soc. 2000, 122, 7849-7850 (b) Printing Small Molecules as Microarrays and Detecting Protein-Ligand Interactions en Masse, G. MacBeath,... 

Metz, G. Ottleben, H. Vetter, D. Small molecule screening on chemical microarrays, in Methods and Principles in Medicinal Chemistry Vol. 

As we will soon discover, microarray-based technologies have found utility in a number of fields. While DNA arrays are the most technically mature and have the broadest application portfolio, we have witnessed the ever-increasing generation of new kinds of probe arrays antibody, antigen, enzyme, aptamer, carbohydrate, tissue, cell, and small molecule microarrays. The list undoubtedly will continue to expand. We can also describe microarrays in terms of prognostic, diagnostic, and predictive roles. A few examples that examine these applications are provided. 

However, recombinant antibodies may be less stable and have lower binding affinities than monoclonal antibodies (Valle and Jendoubi, 2003). Therefore, in order to fully implement the microarray format, a host of diverse capture agents could be required in addition to antibodies. These include peptides, small molecules, aptamers, ribozymes, or other molecular recognition probes yet to be discovered. However, it is also xmderstandable because of the diverse nature of proteins that additional technologies besides microarrays will be used in proteomics research (Hanash, 2003). 

Kuruvilla EG, Shamji AF, Sternson SM, et al. (2002) Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays. Nature 416 653-657. 

MacBeath, G., Koehler, A.N., Schreiber, S.L. (1999) Printing small molecules as microarrays and detecting protein.Kgand interactions en masse./Aw Chem Soc. 121, 7967-7968... 

In other work, using a range of different protein function microarrays, each fabricated in the form of BCCP fusion proteins as described here, we have been able to monitor a wide range of protein activities, including protein-protein interactions and protein-small molecule interactions, as well as carrying out on-chip phosphorylation assays (6) (see Note 15). 

Falsey, J. R., Renil, M., Park, S., Li, S., and Lam, K. S. (2001) Peptide and small molecule microarray for high throughput cell adhesion and functional assays. Bioconjug. Chem. 12, 346-353. 

G. MacBeath, A. N. Koehler, and S. L. Schreiber, Printing small molecules as microarrays and detecting protein-ligand interactions en masse, J. Am. Chem. Soc. 121, 7967—7968 (1999). 

FIGURE 7 Top-scored metabolite-centric network generated by Ingenuity Pathway Analysis (IPA) describing amino acid metabolism, molecular transport, and small-molecule biochemistry. Microarray results were overlaid in the network highlighting associations between metabolites and transcripts in different canonical pathways (CP). Underlined molecules were downregulated not underlined molecules were upregulated Alp, p70 S6k, and AMPK (marked with an asterisk) were not altered. Reproduced from Ref. (20). 

Functional protein microarrays are useful for direct analysis of biochemical activity (e.g., substrate specificity, Refs. 98 and 99), protein protein interaction (100), or small molecule protein interaction. Proteins of interest are over expressed and applied in pure form on addressable arrays, and assays performed (101). 

Figure 7 Protein microarrays and their applications. Ligands, such as proteins, peptides, antibodies, antigens, allergens, and small molecules, are immobilized in high density on modified surfaces to form functional and analytical protein microarrays. These protein microarrays can also be used for various kinds of biochemical analysis.

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