Abstract
Two methods that use chemoselective ligation chemistry to prepare peptide and smallmolecule microarrays are described here. The first method involves the functionalization of a glass slide with a glyoxylyl group, followed by chemoselective ligation of small molecules or peptides to the functionalized surface via a covalent bond. In the second method, peptides or small molecules are first conjugated to a macromolecular scaffold. The final ligand-scaffold conjugates are then spotted and adsorbed onto the solid surface. Three different assay methods to screen such chemical microarrays are described.
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References
Fodor, S. P., Read, J. L., Pirrung, M. C., Stryer, L., Lu, A. T., and Solas, D. (1991) Light-directed, spatially addressable parallel chemical synthesis. Science 251, 767–773.
Pirrung, M. (2002) How to make a DNA chip. Angew. Chem. Int. Ed. 41, 1276–1289.
Schena, M., Shalon, D., Davis, R. W., and Brown, P. O. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467–470.
Wilson, D. S. and Nock, S. (2003) Recent developments in protein microarray technology. Angew. Chem. Int. Ed. 42, 494–500.
Kodadek, T. (2001) Protein microarrays: prospects and problems. Chem. Biol. 8, 105–115.
Xu, Q. and Lam, K. S. (2003) Protein and chemical microarrays-powerful tools for proteomics. J. Biomed. Biotech. 5, 257–266.
Lam, K. S. and Renil, M. (2002) From combinatorial chemistry to chemical microarray. Curr. Opin. Chem. Biol. 6, 353–358.
Wang, D., Liu, S., Trummer, B. J., Deng, C., and Wang, A. (2002) Carbohydrate microarrays for the recognition of cross-reactive molecular markers of microbes and host cells. Nat. Biotechnol. 20, 275–281.
Xu, Q., Miyamoto, S., and Lam, K. S. (2004) A novel approach to chemical microarray using ketone-modified macromolecular scaffolds: application in micro cell-adhesion assay. Mol. Divers. 8(3), 301–310.
Marik, J., Xu, Q., Wang, X., Peng, L., and Lam, K. S. (2004) A novel encoded high-density chemical microarray platform for proteomics and drug development. In Peptides; Peptide Revolution: Genomics, Proteomics ⇐p; Therapeutics; Proceedings of 18th American peptide Symposium (Chorev, M. and Sawyer, T. K., eds.), American Peptide Society, Boston, MA.
Pellois, J. P., Wang, W., and Gao, X. (2000) Peptide synthesis based on t-Boc chemistry and solution photogenerated acids. J. Comb. Chem. 2, 355–360.
Pellois, J. P., Zhou, X., Srivannavit, O., Zhou, T., Gulari, E., and Gao, X. (2002) Individually addressable parallel peptide synthesis on microchips. Nat. Biotechnol. 20, 922–926.
LeProust, E., Pellois, J. P., Yu, P., et al. (2000) Digital light-directed synthesis. A microarray platform that permits rapid reaction optimization on a combinatorial basis. J. Comb. Chem. 2, 349–354.
Gao, X., LeProust, E., Zhang, H., et al. (2001) A flexible light-directed DNA chip synthesis gated by deprotection using solution photogenerated acids. Nucleic Acids Res. 29, 4744–4750.
Singh-Gasson, S., Green, R. D., Yue, Y., et al. (1999) Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat. Biotechnol. 17, 974–978.
Frank, R. (2002) The SPOT-synthesis technique. Synthetic peptide arrays on membrane Supports—principles and applications. J. Immunol. Methods 267, 13–26.
Aina, O. H., Sroka, T. C., Chen, M. L., and Lam, K. S. (2002) Therapeutic cancer targeting peptides. Biopolymers 66, 184–199.
Song, A., Wang, X., Zhang, J., Marik, J., Lebrilla, C. B., and Lam, K. S. (2004) Synthesis of hydrophilic and flexible linkers for peptide derivatization in solid phase. Bioorg. Med. Chem. Lett. 14, 161–165.
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.
Marcaurelle, L. A., Shin, Y., Goon, S., and Bertozzi, C. R. (2001) Synthesis of oxime-linked mucin mimics containing the tumor-related T(N) and sialyl T(N) antigens. Org. Lett. 3, 3691–3694.
Salisbury, C. M., Maly, D. J., and Ellman, J. (2002) Peptide microarrays for the determination of protease substrate specificity. J. Am. Chem. Soc. 124, 14,868–14,870.
Ulman, A. (1996) Formation and structure of self-assembled monolayers. Chem. Rev. 96, 1533–1554.
Xu, Q. and Lam, K. S. (2002) An efficient approach to prepare glyoxylyl functionality on solid-support. Tetrahedron Lett. 43, 4435–4437.
Xu, Q., Miyamoto, S., and Lam, K. S. (2004) A novel approach to chemical microarray using ketone-modified macromolecular scaffolds: application in micro celladhesion assay. Mol. Divers. 8, 301–310;.
Acknowledgments
The authors would like to thank Amanda Enstrom for the assistance with the manuscript. This work was supported by NSF Grant MCB9728399, and NIH Grants R33CA-86364, R33CA-89706, and R01CA-098116.
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Marik, J., Lam, K.S. (2005). Peptide and Small-Molecule Microarrays. In: Zanders, E.D. (eds) Chemical Genomics. Methods in Molecular Biology™, vol 310. Humana Press. https://doi.org/10.1007/978-1-59259-948-6_15
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DOI: https://doi.org/10.1007/978-1-59259-948-6_15
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