Abstract
The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.
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Selected References
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- Crick F. H., Griffith J. S., Orgel L. E. CODES WITHOUT COMMAS. Proc Natl Acad Sci U S A. 1957 May 15;43(5):416–421. doi: 10.1073/pnas.43.5.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cwirla S. E., Peters E. A., Barrett R. W., Dower W. J. Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6378–6382. doi: 10.1073/pnas.87.16.6378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellington A. D., Szostak J. W. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990 Aug 30;346(6287):818–822. doi: 10.1038/346818a0. [DOI] [PubMed] [Google Scholar]
- Fodor S. P., Read J. L., Pirrung M. C., Stryer L., Lu A. T., Solas D. Light-directed, spatially addressable parallel chemical synthesis. Science. 1991 Feb 15;251(4995):767–773. doi: 10.1126/science.1990438. [DOI] [PubMed] [Google Scholar]
- Geysen H. M., Meloen R. H., Barteling S. J. Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3998–4002. doi: 10.1073/pnas.81.13.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houghten R. A., Pinilla C., Blondelle S. E., Appel J. R., Dooley C. T., Cuervo J. H. Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature. 1991 Nov 7;354(6348):84–86. doi: 10.1038/354084a0. [DOI] [PubMed] [Google Scholar]
- Lam K. S., Salmon S. E., Hersh E. M., Hruby V. J., Kazmierski W. M., Knapp R. J. A new type of synthetic peptide library for identifying ligand-binding activity. Nature. 1991 Nov 7;354(6348):82–84. doi: 10.1038/354082a0. [DOI] [PubMed] [Google Scholar]
- Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
- Tuerk C., Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990 Aug 3;249(4968):505–510. doi: 10.1126/science.2200121. [DOI] [PubMed] [Google Scholar]