They took the less traveled road

Excited to share our latest publication! DNA-encoded libraries (DELs) have revolutionized screening and library synthesis. But why stop there? If DELs make it easier, why not use them to explore unconventional areas of molecular diversity?

Arthur Gonse Gonse and Jelena Gaji? Gaji? rose to the challenge with an ambitious mission: to identify ligands for Pleckstrin Homology (PH) domains, which typically bind phosphoinositol lipids—far from ideal starting points for traditional MedChem.

Their work paid off, uncovering binders surprisingly good selective for mSin1, a PH domain exclusively associated with mTORC2. This selectivity is especially impressive given the hundreds of PH domains expressed at any given time. Proteomics revealed that mSin1 was the only one meaningfully enriched.

I’ll let you dive into the details if you're interested: https://doi.org/10.1021/acschembio.4c00597, but for now, a huge congratulations to Arthur and Jelena for navigating uncharted chemical space and tackling such a challenging target class. ????

Stay tuned for the cover!