High-throughput sequencing for the identification of binding molecules from DNA-encoded chemical libraries
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2010-07, Vol.20 (14), p.4188-4192 |
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| creator | Buller, Fabian Steiner, Martina Scheuermann, Jörg Mannocci, Luca Nissen, Ina Kohler, Manuel Beisel, Christian Neri, Dario |
| description | DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after selection. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries.
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs. |
| doi_str_mv | 10.1016/j.bmcl.2010.05.053 |
| format | Article |
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DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs.</description><subject>Biological and medical sciences</subject><subject>Combinatorial Chemistry Techniques</subject><subject>DNA - chemistry</subject><subject>DNA-encoded chemical library</subject><subject>Drug discovery</subject><subject>High-throughput sequencing</subject><subject>Illumina</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Pharmacology. 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The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after selection. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries.
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20538458</pmid><doi>10.1016/j.bmcl.2010.05.053</doi><tpages>5</tpages></addata></record> |
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| subjects | Biological and medical sciences Combinatorial Chemistry Techniques DNA - chemistry DNA-encoded chemical library Drug discovery High-throughput sequencing Illumina Medical sciences Miscellaneous Pharmacology. Drug treatments |
| title | High-throughput sequencing for the identification of binding molecules from DNA-encoded chemical libraries |
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