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Giant Glycosidase Inhibitors: First‐ and Second‐Generation Fullerodendrimers with a Dense Iminosugar Shell
Author(s) -
Nierengarten JeanFrançois,
Schneider Jérémy P.,
Trinh Thi Minh Nguyet,
Joosten Antoine,
Holler Michel,
Lepage Mathieu L.,
Bodlenner Anne,
GarcíaMoreno M. Isabel,
Ortiz Mellet Carmen,
Compain Philippe
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705600
Subject(s) - iminosugar , glycoside hydrolase , chemistry , dendrimer , grafting , glycan , limiting , eyelash , combinatorial chemistry , stereochemistry , nanotechnology , enzyme , biochemistry , materials science , organic chemistry , polymer , biology , glycoprotein , mechanical engineering , genetics , engineering
The multivalent effect in glycosidase inhibition is a new topic in glycoscience that has emerged a few years ago, with the discovery of neoglycoclusters displaying strong binding enhancements over the corresponding monovalent inhibitor. Iminosugar–fullerene conjugates with high valencies have been prepared from iminosugar‐terminated dendrons and a clickable fullerene hexa‐adduct scaffold. The simultaneous grafting of twelve dendrons allows for a very fast dendritic growth thus limiting the number of synthetic steps required to prepare compounds with a high number of peripheral units. The grafting of first‐ and second‐generation dendrons provided fullerodendrimers surrounded by 36 and 108 peripheral iminosugars, respectively. Inhibition studies have been carried out with a panel of glycosidases. In the particular case of Jack bean α‐mannosidase, the 108‐valent nanoconstruct displays inhibition in the nanomolar range and an additional binding enhancement of one order of magnitude when compared to the 36‐valent analogues.