Unusual backfolded binding poses of BAZ2A bromodomain binders
Andrea Dalle Vedove, Giulia Cazzanelli, Vito Giuseppe D’Agostino, Pablo Andres Vargas Rosales, Amedeo Caflisch, Graziano Lolli · 2026
Read Unusual backfolded binding poses of BAZ2A bromodomain binders by Andrea Dalle Vedove, Giulia Cazzanelli, Vito Giuseppe D’Agostino, Pablo Andres Vargas Rosales, Amedeo Caflisch, Graziano Lolli (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13317689.txt.
Description
Andrea Dalle Vedove and co-authors report, in 2026, an unusual folded shape adopted by compounds that bind a hard-to-drug protein domain. BAZ2A helps silence ribosomal DNA and is overproduced in aggressive prostate cancer. Its bromodomain, a pocket that reads chemical marks on proteins, has resisted strong inhibitors because the pocket is shallow.
The team found binders that curl back on themselves into an almost enclosed pose inside the pocket. Such backfolded binding was unexpected for this family of compounds. The authors suggest the pose offers a starting point for ring-shaped macrocyclic inhibitors, a strategy that has worked for other bromodomains. Their structural observations may guide chemists seeking the first potent and selective BAZ2A blockers for cancer research.
Catalog record
| CREATOR | Andrea Dalle Vedove, Giulia Cazzanelli, Vito Giuseppe D’Agostino, Pablo Andres Vargas Rosales, Amedeo Caflisch, Graziano Lolli |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 14 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |