Sulfonylurea Bioisosteres of Sulfonic Acid in JFD 00458‐Based ST6GAL1 Inhibitors Enhance Membrane Permeability
Natan Koraj, Sushmaa Dangudubiyyam, Adelyn M Betances‐Mora, Ema Faganeli, Anne Harduin‐Lepers, Jesús Angulo, Tan Khanh Nguyen, María Bort‐Griñó, Ramon Hurtado‐Guerrero, Marko Anderluh · 2026
Read Sulfonylurea Bioisosteres of Sulfonic Acid in JFD 00458‐Based ST6GAL1 Inhibitors Enhance Membrane Permeability by Natan Koraj, Sushmaa Dangudubiyyam, Adelyn M Betances‐Mora, Ema Faganeli, Anne Harduin‐Lepers, Jesús Angulo, Tan Khanh Nguyen, María Bort‐Griñó, Ramon Hurtado‐Guerrero, Marko Anderluh (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/PMC13512776.txt.
Description
Koraj and colleagues redesigned inhibitors of ST6GAL1 to fix their flaw: they could not cross cell membranes. ST6GAL1 is an enzyme that decorates cell surfaces with sialic acid and helps cancers spread and hide from immunity. Their 2026 medicinal chemistry study started from a known non-sugar inhibitor bearing a sulfonic acid group. They replaced that group with look-alike substitutes called bioisosteres.
Koraj found that sulfonylurea substitutes restored passive membrane crossing in an artificial membrane test while keeping enzyme inhibition. An expanded series improved potency, with the best compound reaching low micromolar strength. Binding measurements confirmed the new compounds engage the enzyme at similar strength to the parent. Magnetic resonance mapping showed which parts of the molecule touch the enzyme, with the strongest inhibitors making extra contacts through their aromatic arms. The work supplies a design framework for cell-permeable versions of this cancer target.
Catalog record
| CREATOR | Natan Koraj, Sushmaa Dangudubiyyam, Adelyn M Betances‐Mora, Ema Faganeli, Anne Harduin‐Lepers, Jesús Angulo, Tan Khanh Nguyen, María Bort‐Griñó, Ramon Hurtado‐Guerrero, Marko Anderluh |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 33 KB |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |