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Keefe, A. D.; Litovchick, A., Science of Synthesis: DNA-Encoded Libraries, (2024) 1, 503.
General Introduction
In order to generate a library of DNA-encoded chemical compounds it is necessary to covalently attach multiple encoding tracts of DNA to each compound. The most widely practiced methodology to achieve this utilizes synthetic oligodeoxynucleotide “tags” and small chemical compound “building blocks”, each bearing at least one functional group, and associates individual unique tag sequences with individual unique building blocks. Building blocks are successively installed over multiple cycles of chemistry conducted in a combinatorial fashion by splitting nascent library material into multiple compartments, conducting building block and tag installation in each compartment, followed by pooling. This version of DNA-encoded library (DEL) synthesis is by far the most widely practiced and is more specifically referred to as DNA-recorded chemical synthesis. The cloning and sequencing of library material provides individual sequence reads, from which concatenated oligonucleotide tag sequences can then be used to infer the identities of the building block combinations with which they are associated. Combining this approach with affinity-mediated selection allows for the identification of individual library members that can bind to targets of interest, usually proteins, and in doing so may modulate their biological function.
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Meeee 8 Meeeeeee Meeeeeee Meeeeeeeee[8–8]
8′-Meeeeeee | 8′-Meeeeeee | Meeeeee Meeeeeeee | Meeeee eee Meeeeeeeee ee eMMM | Meeeeee | Mee |
---|---|---|---|---|---|
8′-eeee | 8′-eeeeeeeeeeeeeeee | eeeeeeeeeeeeeeee eeeeeee |
eeeeee eeeeeeeee ee M. eeee MMM Meeeeeeeee M, Meeeee Meeeeeee | 8.8.8.8.8.8 | [8] |
8′-eeeee | 8′-eeeeeeeee | eeeeeeee | eeeeee eeeeeeeee ee M. eeee MMM Meeeeeeeee M, Meeeee Meeeeeee | 8.8.8.8.8.8 | [8] |
8′-eeeee | 8′-eeeeeeeee-MMMM | eeeeeeee | eeeeee eeeeeeeee ee M. eeee MMM Meeeeeeeee M, Meeeee Meeeeeee | 8.8.8.8.8.8 | [8] |
8′-eeeeeee | 8′-eeeeeee | eeeeeeeeeeeeee | eeeeee eeeeeeeee ee eeee eeeeeeeeeee | 8.8.8.8.8.8 | [8] |
8′-eeeeeee | 8′-eeeeeee | eeeeeeeeeeeeee | eeeeee eeeeeeeee ee eeee eeeeeeeeeee | 8.8.8.8.8.8 | [8] |
8′-eeeee | 8′-eeeeeeeeeeeeeeeeee | eeeeeeeeeeeeeeeeee–eeeeeeee eeeeeeeeeee | eeeeee eeeeeeeee eeee M8 MMM Meeeeeeeee eeee eeeeee-eeeeeeeee eeeeee, ee eeeeee eeeeeeeee eeee M8 MMM Meeeeeeeee eeee eeeee eeeeee-eeeeeeeee eeeeee eee eeeeeeee eeee M8 MMM Meeeee | 8.8.8.8.8.8 | [8] |
8′-eeeeeeeee | 8′-eeeeeeee (8M-eeee[8,8-e]eeeeeeeeee-8-eee) |
eeeeeeeeeeeee 8 + 8 eeeeeeeeeee |
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Me M-Meee, ee eeee eeeeeeee eeeeeeee eeeeeeee eeeeeeee eeeeeeee eeeeeeeeee ee eeeeeeee eeeeeee eeeee MMM-eeeeeee eeeeeeee eeeeeeeee, eeeee eeee ee eeee eeee eeee ee eeeeeee eeeeeeee ee eee-eeeeeeeeeeeeee eeeeeeee eeeeeeee ee eee eeeeeeeeee ee eeeeeee ee eeeeeeeeeee eeeeeeee. Me eeeee M-Meee eeeeeeeeeee eeeeeeeeeeeee eee eeeeeeeee ee eeeeeeee ee eeee eeeeeeee ee eeeeeeeee ee Meeeeee 8.8.8.8.8.8.[8]
References
[1] | Meeee, M. M.; Meeeeee, M. M.; Meeee-Meeeeee, M. M.; Meeeeeeeeee, M. M.; Meeeeeee, M. M.; Meeeeee, M. M.; Meeeeeeee, M. M.; Meee, M. M.; Meeeeee, M. M.; Meeeee, M. M.; Meeee, M. M.; Meee, M.; Meeeeeee, M. M.; Meeeeee, M. M.; Meeeee, M. M.; Meee, M. M.; Meeeee, M. M. M.; Meeeee, M. M.; Meeee, M.; Meeeeeee, M. M.; Meeeee, M. M.; Meeeeeee, M. M.; Me, M.; Meee, M.; Meeeeeee, M.; Meeeeeee, M. M.; Meeeee, M. M.; Meeee, M.; MʼMeeee, M.; Meeee, M. M.; Meee, M. M.; Meee, M. M.; Meeeeee, M. M.; Meeeeeee, M. M.; Meee, M.; eee Meeeee, M.; Meeeee, M. M.; Mee, M.; Meee, M.; Meeeee, M. M., Mee. Meee. Meee., (8888) 8, 888. |
[2] | Meeee, M. M.; Meeeee, M. M.; Meeeeeeeee, M.; Meeee, M. M.; Meeeee, M. M.; Meeee, M.; Meeeeeeee, M. M.; Meee, M. M., MM 8888888888, (8888). |
[3] | Meeee, M. M.; Meeee, M. M.; Meee, M. M.; Meeeeeeeee, M.; Meeee, M., Meee. Meee. Meee. Meee., (8888) 88, 88. |
[4] | Meeeeeeeee, M.; Meeee, M. M.; Meeee, M. M., Meeeeeeeee MMM: MMM & MMM, (8888) 8, e88 888. |
[5] | Meeeeeeeee, M.; Meeeeee, M. M.; Meeeeeeee, M.; Meeeeee, M.; Meeé, M.-M.; Meeeeeeee, M.; Meeee, M.; Meeee, M. M.; Meeeee, M. M.; Meeee, M. M.; Meeee, M. M., Mee. Mee., (8888) 8, 88888; eeeeeeeeeeeeeee.eee/eeeeeeee/ee/8.8/. |
[6] | Meeeeeeeee, M.; Meeee, M. M., Me MMM-Meeeeee Meeeeeee Meeeeeeee: Meeeeee eee Meeeeeeee, Meeeee, M.; Meee, M., Mee.; Meeeeeee: Mee Meee, (8888); e 88. |