A self-assembled multivalent glycosidase inhibitor based on perylene bisimide-deoxynojirimycin conjugates was constructed, inhibited α-mannosidase and exhibited a K value of 38 nM, increased approximately 2763-fold compared with the control drug (miglitol). Furthermore, the postprandial blood glucose (PBG) level in mice of PBI-DNJ was firstly studied. PBI-DNJ exhibited a hypoglycaemic effect in vivo. Importantly, this work developed a new means to explore the hypoglycaemic effect in mice based on self-assembled glycosidase inhibitors.
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http://dx.doi.org/10.1039/c8tb03122c | DOI Listing |
Molecules
January 2025
Université de Reims Champagne-Ardenne, CNRS, ICMR, 51097 Reims, France.
A straightforward synthetic route towards DAB-1 scaffolded dimeric iminosugars is described here, starting from readily available bis-glycosylamines. The method allows the integration of a variety of linkages (aryl, alkyl, polyethyleneglycol chains) between both iminosugars through the choice of the bis-amine used in the first step. Moreover, an additional substituent (allyl, ethynyl) may be inserted into the structure via nucleophilic addition of an organometallic reagent to the starting bis-glycosylamine.
View Article and Find Full Text PDFCarbohydr Res
February 2025
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. Electronic address:
We investigated the transglycosylation reaction of two types of oligosaccharide acceptors, i.e., β-cyclodextrin (CD) derivatives 1 and 2 conjugated with multiple glucose (Glc) units, catalyzed by endo-β-N-acetyl-glucosaminidase from Mucor hiemalis (Endo-M) using the oligosaccharide donor sialoglycopeptide (SGP).
View Article and Find Full Text PDFArch Biochem Biophys
February 2025
The Division of Structural Biology, The Nuffield Department of Medicine, University of Oxford, UK; The Rosalind Franklin Institute, Harwell Campus, Didcot, OX11 0QS, UK. Electronic address:
Multifunctionality, processivity, and thermostability are critical for the cost-effective enzymatic saccharification of non-food plant biomass polymers such as β-glucans, celluloses, and xylans to generate biofuels and other valuable products. We present molecular insights into a processive multifunctional endo-1,3-1,4-β-d-glucanase (Tt_End5A) from the hyperthermophilic bacterium Thermogutta terrifontis. Tt_End5A demonstrated activities against a broad spectrum of β-polysaccharides, including barley glucan, lichenan, carboxymethyl cellulose, regenerated amorphous cellulose (RAC), Avicel, xylan, laminarin, mannan, curdlan, xanthan, and various chromogenic substrates at pH 7 and temperatures ranging from 70 to 80°C.
View Article and Find Full Text PDFBioconjug Chem
January 2025
Department of Chemistry "Ugo Schiff" (DICUS), University of Florence, Via della Lastruccia 3-13, Sesto Fiorentino, FI 50019, Italy.
The present study reports the preparation of the first multivalent iminosugars built onto a glyco-gold nanoparticle core (glyco-AuNPs) capable of stabilizing or enhancing the activity of the lysosomal enzyme GCase, which is defective in Gaucher disease. An -nonyltrihydroxypiperidine was selected as the bioactive iminosugar unit and further functionalized, via copper-catalyzed alkyne-azide cycloaddition, with a thiol-ending linker that allowed the conjugation to the gold core. These bioactive ligands were obtained with either a linear monomeric or dendritic trimeric arrangement of the iminosugar.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Organic Chemistry, Indian Institute of Science, Bangalore, India. Electronic address:
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