Recent trends in glycodendrimer syntheses and applications.
Carbohydrate protein interactions are at the front of several biological interactions spanning from cell growth and differentiation, cell signaling, apoptosis, cancer, and microbial infections. Classical medicinal glycochemistry has so far concentrated on designing glycosyl transferase and glycohydrolase inhibitors for which only handful candidates have emerged. Added to the complexity of drug resistances, drugs in development have rapidly witnessed this limitation as well. New approaches are therefore highly encouraged. Amongst these, blocking pathogen adhesions to host tissues as an early preventive mechanism is a foreseeable potentiality. It has the clear advantage that the pathogens are unlikely to mutate their anchoring motifs without upsetting their own binding to host tissues. An added dilemma is that these binding interactions are usually too weak to provide suitable drug candidates. As a consequence, the community has successfully come up with multivalent glycoconjugates having greatly enhanced avidity. An alternative strategy in which both monovalent ligands as well as the multivalent scaffolds undergoing QSAR improvement is thus suggested. This review will highlight recent trends toward the design of multivalent glycodendrimers and their biological applications.
Chabre
Yoann M
YM
Department of Chemistry, Université du Québec à Montréal, Montreal (QC), Canada.
Roy
René
R
D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D015195:Drug Design; D006001:Glycoconjugates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship
D050091:Dendrimers; D006001:Glycoconjugates; D006020:Glycopeptides; D008024:Ligands; C104700:PAMAM Starburst; D011073:Polyamines