Science of Synthesis

Prati, L.; Lucaroni, L.; Cazzamalli, S.; Neri, D.; Oehler, S., Science of Synthesis: DNA-Encoded Libraries, (2024) 1, 540.

DNA-encoded chemical libraries (DELs) are powerful tools for the isolation of binders against proteins of pharmaceutical interest. The probability of identifying ligands for a certain protein target correlates with the size, purity, and chemical diversity of the screened library.[‌47‌] Encoded self-assembling chemical (ESAC) and dynamic libraries hold the promise to reach high numbers of library members at exceptional purity due to the encoded combinatorial assembly of separately synthesized sublibraries. Moreover, in contrast with conventional DELs, dual-pharmacophore libraries can simultaneously bind different pockets or surfaces, thus enhancing the affinity towards the target protein.[‌48‌] Dual-display libraries have been successfully implemented for the discovery of de novo ligands and for affinity maturation applications.[‌6‌,‌10‌,‌14‌] Success stories include the identification of AAZ+, a highly potent ligand for carbonic anhydrase IX, which has shown diagnostic and therapeutic potential for renal cell carcinoma in preclinical cancer models.[‌6‌,‌27‌]

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References