Expanding the DNA-encoded library toolbox: identifying small molecules targeting RNA.

ABSTRACT: DNA-encoded library (DEL) technology is a powerful tool for small molecule identification in drug discovery, yet the reported DEL selection strategies were applied primarily on protein targets in either purified form or in cellular context. To expand the application of this technology, we employed DEL selection on an RNA target HIV-1 TAR (trans-acting responsive region), but found that the majority of signals were resulted from false positive DNA-RNA binding. We thus developed an optimized selection strategy utilizing RNA patches and competitive elution to minimize unwanted DNA binding, followed by k-mer analysis and motif search to differentiate false positive signal. This optimized strategy resulted in a very clean background in a DEL selection against Escherichia coli FMN Riboswitch, an

SUBMITTER: Chen Q 

PROVIDER: S-EPMC9262588 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature