Structural highlights
Function
Q8A3I4_BACTN
Publication Abstract from PubMed
Fucosidase inhibition shows potential in numerous therapeutic contexts. Substitution of fucose-like iminosugars with hydrophobic "aglycons" yields significant improvements in potency of fucosidase inhibition. Here we have prepared three new 2-aryl-3,4-dihydroxy-5-methylpyrrolidines featuring phenyl substituents in variable orientations with respect to the iminocyclitol core and at various distances from it to explore the key binding interactions that stabilise the enzyme-inhibitor complex. The presence of a triazole linker in one structure resulted in nanomolar inhibition of the fucosidase from bovine kidney (Ki =4.8 nM), thus giving rise to one of the most potent pyrrolidine-type inhibitors of this enzyme known to date.
Exploiting the Hydrophobic Terrain in Fucosidases with Aryl-Substituted Pyrrolidine Iminosugars.,Hottin A, Wright DW, Davies GJ, Behr JB Chembiochem. 2014 Nov 26. doi: 10.1002/cbic.201402509. PMID:25427942[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hottin A, Wright DW, Davies GJ, Behr JB. Exploiting the Hydrophobic Terrain in Fucosidases with Aryl-Substituted Pyrrolidine Iminosugars. Chembiochem. 2014 Nov 26. doi: 10.1002/cbic.201402509. PMID:25427942 doi:http://dx.doi.org/10.1002/cbic.201402509