Multivalent Effect in Glycosidase Inhibition: The End of the Beginning. Issue 1 (17th April 2019)

• Record Type: Journal Article
• Authors: Compain, Philippe
• Is Part Of: Chemical record. Volume 20:Issue 1(2020)
• Page Start: 10
• Page End: 22
• Publication Date: 2019-04-17
• Subjects: cluster compounds -- inhibitors -- carbohydrates -- click chemistry -- biological activities; Chemistry -- Periodicals; 540
• DOI: 10.1002/tcr.201900004
• Languages: English
• ISSNs: 1527-8999

Abstract

Abstract: Glycosidases are ubiquitous enzymes involved in a diversity of key biological processes such as energy uptake or cell wall degradation. The design of specific glycosidase inhibitors has been therefore the subject of intense research efforts in academia and pharmaceutical industry. However, until recently, the study of the impact of multivalency on glycosidase inhibition was almost completely neglected. The following account will review our ten year journey on the design of multivalent glycomimetics within our research group, from the discovery of the first strong multivalent effect in glycosidase inhibition to the high‐resolution crystal structures of Jack bean α‐mannosidase in complex with the multimeric inhibitor displaying the largest binding enhancements reported so far. Abstract : This account reviews a sweet adventure in the field of giant glycomimetics from the discovery of the first strong multivalent effect in glycosidase inhibition to the high‐resolution crystal structures of a model α‐mannosidase in complex with the multimeric inhibitor displaying the largest binding enhancements ever reported for an enzyme inhibitor.