(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

Abstract

SummaryOligosaccharides are currently recognised as having functions that influence the entire spectrum of cell activities. However, a distinct disadvantage of naturally occurring oligosaccharides is their metabolic instability in biological systems. Therefore, much effort has been spent in the past two decades on the development of feasible routes to carbohydrate mimetics which can compete with their O-glycosidic counterparts in cell surface adhesion, inhibit carbohydrate processing enzymes, and interfere in the biosynthesis of specific cell surface carbohydrates. Such oligosaccharide mimetics are potential therapeutic agents against HIV and other infections, against cancer, diabetes and other metabolic diseases. An efficient strategy to access this type of compounds is the replacement of the glycosidic linkage by amide or pseudoamide functions such as thiourea, urea and guanidine. In this review we summarise the advances over the last decade in the synthesis of oligosaccharide mimetics that possess amide and pseudoamide linkages, as well as studies focussing on their supramolecular and recognition properties.

Cyclodextrin-based multivalent glycodisplays: covalent and supramolecular conjugates to assess carbohydrate–protein interactions

“…By exploiting the thiourea-forming coupling reaction 44,45 between isothiocyanate-armed glycodendrons and mono-(C-6)-amino bCD, they prepared a series of aMan-coated conjugates comprising valencies between 2 and 6 ( Fig. 3).…”

Sugar‐Modified Foldamers as Conformationally Defined and Biologically Distinct Glycopeptide Mimics

“…[6] The study of foldamers has in the past helped enlighten our understanding of the origins of the preferred secondary structures and biological activities of biopolymers. [7] Considering the endogenous and therapeutic importance of glycoproteins, we were struck by the dearth of reports describing the impact of glycosylation on the secondary structures of peptide foldamers.…”

Click Synthesis of Size- and Shape-Tunable Star Polymers with Functional Macrocyclic Cores for Synergistic DNA Complexation and Delivery

“…First, isothiocyanates react with amines to produce thiourea adducts without byproducts; the reaction is highly efficient without need of catalyst and insensitive to oxygen and moisture, meeting all the criteria of click chemistry . Second, the achiral character of the thiourea bridge greatly simplifies the preparation of glyco­oligomers, avoiding cumbersome diastereomer separations typical of classical oligosaccharide syntheses . Third, the resulting thiourea segments provide anchoring centers for metal chelation and hydrogen bonding which has been extensively used in organocatalysis − as well as supramolecular and medicinal chemistry Canonic n -meric cyclotrehalans ( CT n ) alternating from two to five α,α′-trehalose and thiourea moieties ( CT2 to CT5 ) are currently on record (Figure A). , In this work we have focused on dimeric ( CT2 ) and trimeric ( CT3 ) functional cores, with respectively 12 and 18 hydroxyl groups in their canonic form (Figure A) that can serve as chain initiators for star polymer construction.…”