The synthesis and lectin-binding properties of novel mannose-functionalised polymers

Charville, Hayley; Jin, Jianyong; Evans, Clive W.; Brimble, Margaret A.; Williams, David E.

doi:10.1039/c3ra42781a

Cited by 7 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…39 Recently, a carbohydrate-functionalized polymer synthesized by Charville et al demonstrated that copolymers containing a higher degree of mannose functionalization were more prone to binding lectin receptors. 40 Our method which includes the functionalization with mannose alkyne linker synthesized by bismuth(V)-mediated activation of a thioglycoside has yielded pentablock copolymers with hydrophobic polyoxyproplyene blocks that self-assemble into micelles. These pentablock copolymers are capable of condensing DNA for gene delivery through tertiary amine groups in the outer blocks.…”

Section: Further Discussionmentioning

confidence: 99%

Synthesis and functionalization of virus-mimicking cationic block copolymers with pathogen-associated carbohydrates as potential vaccine adjuvants

et al. 2014

View full text Add to dashboard Cite

We report the synthesis of a family of amphiphilic pentablock polymers with different cationic blocks and with controlled architectures as potential vaccine carriers for subunit vaccines. The temperature and pHdependent micellization and gelation of these pentablock copolymers can provide a depot for sustained protein and gene delivery. The amphiphilic central triblock promotes cellular endocytosis, good gene delivery and has been used effectively as a vaccine adjuvant. The pentablock copolymer outer blocks condense DNA spontaneously as a result of electrostatic interactions for sustained combinational therapy. This family of polymers with different cationic groups was evaluated based on DNA complexation-ability and cytotoxicity to select promising candidates as DNA-based subunit vaccine adjuvants. Modification of other polymer systems with carbohydrates like mannose has been shown to enhance immunogenicity by activating pattern recognition receptors on antigen presenting cells and increasing uptake in these cells. Here, we report the synthesis of a virus-mimicking pentablock copolymer vaccine platform by successful functionalization of these polymers with mannose through an azide-alkyne Huisgen cycloaddition. The synthesis of a mannoside with the alkyne linker was achieved by a recently reported bismuth(V)-mediated activation of a thioglycoside that proved to leave the alkyne intact. The carbohydrate modification was shown not to interfere with the ability of these virus-mimicking block copolymers to complex DNA, thereby making this family of modified materials promising candidates for DNA-based vaccine delivery. Disciplines

show abstract

Section: Further Discussionmentioning

confidence: 99%

Synthesis and functionalization of virus-mimicking cationic block copolymers with pathogen-associated carbohydrates as potential vaccine adjuvants

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The synthesis of AmB–EMCH was achieved as summarized in Scheme S2 . AmB was let to react with 4-acetylbenzoic acid, to yield AmB-bz as previously reported [ 29 ]. Subsequently, AmB-bz (50 mg, 0.047 mmol) was dissolved in dry MeOH (0.6 mL) and combined under inert atmosphere (Ar) with EMCH trifluoroacetic acid salt (33.92 mg, 0.099 mmol).…”

Section: Methodsmentioning

confidence: 99%

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

et al. 2020

View full text Add to dashboard Cite

Macrophages are hosts for intracellular pathogens involved in numerous diseases including leishmaniasis. They express surface receptors that may be exploited for specific drug-targeting. Recently, we developed a PEGylated dendritic polyglycerol-based conjugate (PG–PEG) that colocalizes with intracellular parasite. We hereby study the effect of surface decoration with mannose units on the conjugates’ targeting ability toward leishmania intracellular parasites. Murine and human macrophages were exposed to fluorescently labeled mannosylated PG–PEG and uptake was quantified by flow cytometry analysis. Nanocarriers bearing five mannose units showed the highest uptake, which varied between 30 and 88% in the population in human and murine macrophages, respectively. The uptake was found to be dependent on phagocytosis and pinocytosis (80%), as well as clathrin-mediated endocytosis (79%). Confocal microscopy showed that mannosylated PG–PEGs target acidic compartments in macrophages. In addition, when both murine and human macrophages were infected and treated, colocalization between parasites and mannosylated nanoconjugates was observed. Leishmania-infected bone marrow-derived macrophages (BMM) showed avidity by mannosylated PG–PEG whereas non-infected macrophages rarely accumulated conjugates. Moreover, the antileishmanial activity of Amphotericin B was kept upon conjugation to mannosylated PG–PEG through a pH-labile linker. This study demonstrates that leishmania infected macrophages are selectively targeted by mannosylated PEGylated dendritic conjugates.

show abstract

“…an increase in the degree of glycosylation normally gives rise to enhanced saccharide-lectin interactions. 6,[14][15][16][17][18] Finally, the relative spatial orientation of the saccharide recognition elements and the structural features of the substrates upon which the saccharide residues are displayed also have great inuence. 19,20 In this case, hyperbranched, a-helix glycopolymers could be designed to adjust biological status when exposed to carbohydrate receptors.…”

Section: Introductionmentioning

confidence: 99%

Glycosylation of polyphosphazenes by thiol-yne click chemistry for lectin recognition

et al. 2015

View full text Add to dashboard Cite

show abstract

The synthesis and lectin-binding properties of novel mannose-functionalised polymers

Cited by 7 publications

References 35 publications

Synthesis and functionalization of virus-mimicking cationic block copolymers with pathogen-associated carbohydrates as potential vaccine adjuvants

Synthesis and functionalization of virus-mimicking cationic block copolymers with pathogen-associated carbohydrates as potential vaccine adjuvants

Mannose-Decorated Dendritic Polyglycerol Nanocarriers Drive Antiparasitic Drugs To Leishmania infantum-Infected Macrophages

Glycosylation of polyphosphazenes by thiol-yne click chemistry for lectin recognition

Contact Info

Product

Resources

About