Carbon-based glyco-nanoplatforms: towards the next generation of glycan-based multivalent probes

Abstract

Cell surface carbohydrates mediate a wide range of carbohydrate-protein interactions key to healthy and disease mechanisms. Many of such interactions are multivalent in nature and in order to study these processes at a molecular level, many glycan-presenting platforms have been developed over the years. Among those, carbon nanoforms such as graphene and their derivatives, carbon nanotubes, carbon dots and fullerenes, have become very attractive as biocompatible platforms that can mimic the multivalent presentation of biologically relevant glycosides. The most recent examples of carbon-based nanoplatforms and their applications developed over the last few years to study carbohydrate-mediate interactions in the context of cancer, bacterial and viral infections, among others, are highlighted in this review.

Fig. 1. (A) General principle for graphene and graphene derivatives-based FRET fluorescent glycoprobes used for glycan-binding protein sensing. (B) Structure of aminopyrene-1, dicyanomethylene-2 and 3, and aminocoumarin-4 and 5 glycoside derivatives.

Fig. 2. General structure of mannosyl anthraquinone 6 and the glycoconjugate complex grafted on a GO-coated electrode.

Fig. 3. Representative general structures of sialylglycopeptide-coated graphene via a pyrene (shown in light grey) 7, and sialylgraphene derivatives 8 which features trGO derivatives modified via a triazine moiety bearing a dendrimetic sialic acid conjugate.

Fig. 4. Structure of non-covalently functionalised mannographene derivatives 9 and 10 and covalently bound derivatives 11 and 12.

Fig. 5. (A) Structures of heptamannosylated β-cyclodextrin 13 and 14; (B) supramolecular assembly of cyclodextrin 13 on adamantyl-functionalized trGO to form 15, and (C) supramolecular assembly of cyclodextrin 14 on benzimidazole-functionalized trGO/carbon nitride composite to form 16.

Fig. 6. Structures of glyconanomaterials 16–19. For the sake of clarity, a nanotube fragment with one copy of glycodendron or glycofullerene is shown.

Fig. 7. (A) Chemical structure of the polymer 20a that forms the nanorings. (B) Schematic representation of the FimH adhesin promoted specific interaction of E. coli with 20b. Reproduced with permission from Royal Society of Chemistry.

Fig. 8. Structure of glyconanomaterial 21. For the sake of clarity, a nanotube fragment with one copy of glycoconjugate is shown.

Fig. 9. (A) General structure of glycosidic carbon dots and structure of amino-containing derivatives 22–26; (B) scheme for the functionalisation of CD core to aminoglycoside derivatives.

Scheme 1. Surface functionalisation of 27 to alkyne 28, azide 29, and vinylsulfone 30 derivatives, and glycan coupling to furnish glycoCDs 31–35.

Scheme 2. Synthesis of glyco CDs 36–40via thermal decomposition of ammonium citrate and the respective carbohydrate.

Fig. 10. General representation of glycofullerenes 41–46.

Fig. 11. General representation of mannosylated superballs 47 (with a shorter linker, highlighted in red) and 48 (with a longer linker, highlighted in orange).

Fig. 12. General structures of nanoballs 52–54 and IC₅₀ values for nanoballs in inhibition studies Zika and Dengue-pseudotype virus.

Fig. 13. General representation of glycofullerenes 55–58 and monovalent iminosugar 59 and their corresponding α-Mannoside (JB α-man) inhibitory activities (K_i). *rp = K_i (reference)/K_i DNJ-fullerene, n = number of inhitope units relative to the inhitope number in the reference.

Fig. 14. General representation of compounds 60–63.

Fig. 15. General representation of compounds 64–65.

Fig. 16. Structures of glycofullerenes 66–67.

Javier Ramos-Soriano

Mattia Ghirardello

M. Carmen Galan