4pee › Citations

Exploiting the hydrophobic terrain in fucosidases with aryl-substituted pyrrolidine iminosugars.

Hottin A, Wright DW, Davies GJ, Behr JB
Chembiochem 16 277-83 (2015)
Related entries: 4pcs, 4pct

Cited: 8 times
EuropePMC logo PMID: 25427942

Abstract

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.

Reviews citing this publication (2)

  1. Glycoside Mimics from Glycosylamines: Recent Progress. Nicolas C, Martin OR. Molecules 23 E1612 (2018)
  2. Multivalent Pyrrolidine Iminosugars: Synthesis and Biological Relevance. Wang Y, Xiao J, Meng A, Liu C. Molecules 27 5420 (2022)

Articles citing this publication (6)

  1. N-Guanidino Derivatives of 1,5-Dideoxy-1,5-imino-d-xylitol are Potent, Selective, and Stable Inhibitors of β-Glucocerebrosidase. Sevšek A, Šrot L, Rihter J, Čelan M, van Ufford LQ, Moret EE, Martin NI, Pieters RJ. ChemMedChem 12 483-486 (2017)
  2. Exploring the divalent effect in fucosidase inhibition with stereoisomeric pyrrolidine dimers. Hottin A, Wright DW, Moreno-Clavijo E, Moreno-Vargas AJ, Davies GJ, Behr JB. Org Biomol Chem 14 4718-4727 (2016)
  3. Expanding the library of divalent fucosidase inhibitors with polyamino and triazole-benzyl bridged bispyrrolidines. Hottin A, Carrión-Jiménez S, Moreno-Clavijo E, Moreno-Vargas AJ, Carmona AT, Robina I, Behr JB. Org Biomol Chem 14 3212-3220 (2016)
  4. Orthoester functionalized N-guanidino derivatives of 1,5-dideoxy-1,5-imino-d-xylitol as pH-responsive inhibitors of β-glucocerebrosidase. Sevšek A, Sastre Toraño J, Quarles van Ufford L, Moret EE, Pieters RJ, Martin NI. Medchemcomm 8 2050-2054 (2017)
  5. Arabinoamidine synthesis and its inhibition toward β-glucosidase (sweet almonds) in comparison to a library of galactonoamidines. Pickens JB, Striegler S, Fan QH. Bioorg Med Chem 24 3371-3377 (2016)
  6. A second-generation ferrocene-iminosugar hybrid with improved fucosidase binding properties. Hottin A, Scandolera A, Duca L, Wright DW, Davies GJ, Behr JB. Bioorg Med Chem Lett 26 1546-1549 (2016)


Quick links