Bola‐Amphiphilic Glycodendrimers: New Carbohydrate‐Mimicking Scaffolds to Target Carbohydrate‐Binding Proteins

• Published in: Chemistry : a European journal Vol. 28; no. 58; pp. e202201400 - n/a
• Main Authors: Zhang, Wenzheng, Dhumal, Dinesh, Zhu, Xiaolei, Ralahy, Brigino, Ellert‐Miklaszewska, Aleksandra, Wu, Jing, Laurini, Erik, Yao, Yi‐Wen, Kao, Chai‐Lin, Iovanna, Juan L., Pricl, Sabrina, Kaminska, Bozena, Xia, Yi, Peng, Ling
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 18.10.2022; Wiley Subscription Services, Inc; Wiley-VCH Verlag; John Wiley and Sons Inc
• Subjects: Binding; bola-amphiphiles; Carbohydrates; Carbohydrates - chemistry; Cell surface; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Dendrimers; Dendrimers - chemistry; Glucose; glucose transporters; glycodendrimers; Hydrophobicity; Lectins - chemistry; Mannose; Mannose - chemistry; Mannose receptors; Medicinal Chemistry; Organic chemistry; Physical Sciences; Reactive Oxygen Species; Scaffolds; Science & Technology; targeted delivery; Transport buildings, stations and terminals; glycodendrimers; mannose receptors; LECTIN; JANUS; DENDRIMER; bola-amphiphiles; glucose transporters; targeted delivery; MULTIVALENCY; DELIVERY; mannose-dendrimer; Bola-amphiphiles; glucose-dendrimer
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202201400

Dendrimers are appealing scaffolds for creating carbohydrate mimics with unique multivalent cooperativity. We report here novel bola‐amphiphilic glycodendrimers bearing mannose and glucose terminals, and a hydrophobic thioacetal core responsive to reactive oxygen species. The peculiar bola‐amphiphilic feature enabled stronger binding to lectin compared to conventional amphiphiles. In addition, these dendrimers are able to target mannose receptors and glucose transporters expressed at the surface of cells, thus allowing effective and specific cellular uptake. This highlights their great promise for targeted delivery. Smart dumbbell: Innovative bola‐amphiphilic glycodendrimers with mannose and glucose terminals have been designed and synthesized. They demonstrated stronger binding to the carbohydrate‐binding protein ConA than conventional amphiphilic glycodendrimers thanks to their unique dumbbell‐like structure. In addition, these bola‐dendrimers targeted mannose receptors and glucose transporters for effective cellular uptake, and thus hold great promise in carbohydrate‐binding protein‐targeted drug delivery.