@article {311,
	title = {Enantioselective protein affinity selection mass spectrometry (E-ASMS).},
	journal = {Nat Commun},
	year = {2025},
	month = {2025 Dec 17},
	abstract = {<p>We report an enantioselective protein affinity selection mass spectrometry screening approach (E-ASMS) that enables the detection of weak binders, informs on selectivity, and generates orthogonal confirmation of binding. After method development with control proteins, we screen 31 human proteins against a designed library of 8,217 chiral compounds. We identify 16 binders to 12 targets, including many proteins predicted to be "challenging to ligand", and confirm their interactions through orthogonal biophysical assays. Seven binders to six targets display enantioselective binding, with K values ranging from 3 to 20 {\textmu}M. Binders for four targets (DDB1, WDR91, WDR55, and HAT1) are selected for in-depth characterization using X-ray crystallography. In all four cases, the mechanisms underlying enantioselectivity are readily explained. These results demonstrate that E-ASMS enables the identification and characterization of selective and weakly binding ligands for novel protein targets with unprecedented throughput and sensitivity.</p>},
	issn = {2041-1723},
	doi = {10.1038/s41467-025-67403-2},
	author = {Wang, Xiaoyun and Sun, Jianxian and Ahmad, Shabbir and Yang, Diwen and Li, Fengling and Chan, U Hang and Zeng, Hong and Simoben, Conrad V and Green, Stuart R and Silva, Madhushika and Houliston, Scott and Dong, Aiping and Bolotokova, Albina and Gibson, Elisa and Kutera, Maria and Ghiabi, Pegah and Kondratov, Ivan and Matviyuk, Tetiana and Chuprina, Alexander and Mavridi, Danai and Lenz, Christopher and Joerger, Andreas C and Brown, Benjamin D and Heath, Richard B and Yue, Wyatt W and Robbie, Lucy K and Beyett, Tyler S and M{\"u}ller, Susanne and Knapp, Stefan and Owen, Dafydd R and Harding, Rachel and Schapira, Matthieu and Brown, Peter J and Santhakumar, Vijayaratnam and Ackloo, Suzanne and Arrowsmith, Cheryl H and Edwards, Aled M and Peng, Hui* and Halabelian, Levon*}
}
