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Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion.

Campo VL, Ivanova IM, Carvalho I, Lopes CD, Carneiro ZA, Saalbach G, Schenkman S, da Silva JS, Nepogodiev SA, Field RA - Tetrahedron (2015)

Bottom Line: Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers.The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi.In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP, Brazil.

ABSTRACT

Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

No MeSH data available.


Related in: MedlinePlus

Proposed sialylated products structures 21, 22 and 23 of enzymatic transformation of compound 10. Reagents and conditions: 3 mM fetuin, 1 mM compound 10, T. cruzi trans-sialidase in 100 mM, pH 7.5 phosphate buffer, 28 °C, 9 days.
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sch4: Proposed sialylated products structures 21, 22 and 23 of enzymatic transformation of compound 10. Reagents and conditions: 3 mM fetuin, 1 mM compound 10, T. cruzi trans-sialidase in 100 mM, pH 7.5 phosphate buffer, 28 °C, 9 days.

Mentions: Cyclic compounds 8–10 and 19 were tested for their ability to act as substrates for TcTS,21,40 with fetuin serving as a donor substrate for O-3 sialylation of the galactose residues in the triazole-linked macrocycles. Reactions were carried out over the course of 9 days, with addition of further fetuin and enzyme after 5 days, and addition of fetuin again after 7 days. The reaction mixtures were monitored by TLC and in all cases formation of new compounds was observed, which were identified by HRMS. Thus, reaction of 1,4 triazole-linked cyclic trimer 10 resulted in formation of mono-, di- and tri-sialylated products 21, 22 and 23, respectively (Scheme 4). Related reactivity was observed for 1,4-triazole-linked cyclic dimer 9, which gave two sialylated products, mono-sialylated and di-sialylated derivatives. The 1,4-triazole-linked cyclic monomer 8 and 1,5-triazole-linked cyclic monomer 19 gave mono-sialylated products as expected (see Supplementary data). It is therefore evident that cyclic triazole-linked pseudo-galactooligomers are recognised by, and can act as acceptor substrates for, TcTS.


Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion.

Campo VL, Ivanova IM, Carvalho I, Lopes CD, Carneiro ZA, Saalbach G, Schenkman S, da Silva JS, Nepogodiev SA, Field RA - Tetrahedron (2015)

Proposed sialylated products structures 21, 22 and 23 of enzymatic transformation of compound 10. Reagents and conditions: 3 mM fetuin, 1 mM compound 10, T. cruzi trans-sialidase in 100 mM, pH 7.5 phosphate buffer, 28 °C, 9 days.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542550&req=5

sch4: Proposed sialylated products structures 21, 22 and 23 of enzymatic transformation of compound 10. Reagents and conditions: 3 mM fetuin, 1 mM compound 10, T. cruzi trans-sialidase in 100 mM, pH 7.5 phosphate buffer, 28 °C, 9 days.
Mentions: Cyclic compounds 8–10 and 19 were tested for their ability to act as substrates for TcTS,21,40 with fetuin serving as a donor substrate for O-3 sialylation of the galactose residues in the triazole-linked macrocycles. Reactions were carried out over the course of 9 days, with addition of further fetuin and enzyme after 5 days, and addition of fetuin again after 7 days. The reaction mixtures were monitored by TLC and in all cases formation of new compounds was observed, which were identified by HRMS. Thus, reaction of 1,4 triazole-linked cyclic trimer 10 resulted in formation of mono-, di- and tri-sialylated products 21, 22 and 23, respectively (Scheme 4). Related reactivity was observed for 1,4-triazole-linked cyclic dimer 9, which gave two sialylated products, mono-sialylated and di-sialylated derivatives. The 1,4-triazole-linked cyclic monomer 8 and 1,5-triazole-linked cyclic monomer 19 gave mono-sialylated products as expected (see Supplementary data). It is therefore evident that cyclic triazole-linked pseudo-galactooligomers are recognised by, and can act as acceptor substrates for, TcTS.

Bottom Line: Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers.The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi.In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

View Article: PubMed Central - PubMed

Affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Av. Café S/N, CEP 14040-903, Ribeirão Preto, SP, Brazil.

ABSTRACT

Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.

No MeSH data available.


Related in: MedlinePlus