Unknown

Dataset Information

0

Stereo- and regiodefined DNA-encoded chemical libraries enable efficient tumour-targeting applications.


ABSTRACT: The encoding of chemical compounds with amplifiable DNA tags facilitates the discovery of small-molecule ligands for proteins. To investigate the impact of stereo- and regiochemistry on ligand discovery, we synthesized a DNA-encoded library of 670,752 derivatives based on 2-azido-3-iodophenylpropionic acids. The library was selected against multiple proteins and yielded specific ligands. The selection fingerprints obtained for a set of protein targets of pharmaceutical relevance clearly showed the preferential enrichment of ortho-, meta- or para-regioisomers, which was experimentally verified by affinity measurements in the absence of DNA. The discovered ligands included novel selective enzyme inhibitors and binders to tumour-associated antigens, which enabled conditional chimeric antigen receptor T-cell activation and tumour targeting.

SUBMITTER: Favalli N 

PROVIDER: S-EPMC8405038 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9814293 | biostudies-literature
| S-EPMC8790773 | biostudies-literature
| S-EPMC7673237 | biostudies-literature
| S-EPMC10357458 | biostudies-literature
| S-EPMC6126613 | biostudies-literature
| S-EPMC9298793 | biostudies-literature
| S-EPMC8603192 | biostudies-literature
| S-EPMC7014401 | biostudies-literature
| S-EPMC7156289 | biostudies-literature
| S-EPMC7530011 | biostudies-literature