Tim P Ofman, Jurriaan J A Heming, Alba Nin-Hill, Florian Küllmer, Elisha Moran, Megan Bennett, Roy Steneker, Anne-Mei Klein, Gijs Ruijgrok, Ken Kok, Zach W B Armstrong, Johannes M F G Aerts, Gijsbert A van der Marel, Carme Rovira, Gideon J Davies, Marta Artola, Jeroen D C Codée, Hermen S Overkleeft
Glycoside hydrolases (glycosidases) take part in myriad biological processes and are important therapeutic targets. Competitive and mechanism-based inhibitors are useful tools to dissect their biological role and comprise a good starting point for drug discovery. The natural product, cyclophellitol, a mechanism-based, covalent and irreversible retaining β-glucosidase inhibitor has inspired the design of diverse α- and β-glycosidase inhibitor and activity-based probe scaffolds. Here, we sought to deepen our understanding of the structural and functional requirements of cyclophellitol-type compounds for effective human α-glucosidase inhibition...
April 16, 2024: Chemistry: a European Journal