α-d-Mannoside ligands with a valency ranging from one to three: Synthesis and hemagglutination inhibitory properties

Hussein Al-Mughaid; Maha Khazaaleh

doi:10.1016/j.carres.2021.108396

α-d-Mannoside ligands with a valency ranging from one to three: Synthesis and hemagglutination inhibitory properties

Carbohydr Res. 2021 Oct:508:108396. doi: 10.1016/j.carres.2021.108396. Epub 2021 Jul 8.

Authors

Hussein Al-Mughaid¹, Maha Khazaaleh²

Affiliations

¹ Department of Chemistry, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan. Electronic address: al-mughaid@just.edu.jo.
² Department of Chemistry, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan.

PMID: 34298357
DOI: 10.1016/j.carres.2021.108396

Abstract

Six mono-, di-, and trivalent α-d-mannopyranosyl conjugates built on aromatic scaffolds were synthesized in excellent yields by Cu(I) catalyzed azide-alkyne cycloaddition reaction (CuAAC). These conjugates were designed to have unique, flexible tails that combine a mid-tail triazole ring, to interact with the tyrosine gate, with a terminal phenyl group armed with benzylic hydroxyl groups to avoid solubility problems as well as to provide options to connect to other supports. Biological evaluation of the prepared conjugates in hemagglutination inhibition (HAI) assay revealed that potency increases with valency and the trivalent ligand 6d (HAI = 0.005 mM) is approximately sevenfold better than the best meta-oriented monovalent analogues 2d and 4d (HAI ≈ 0.033 mM) and so may serve as a good starting point to find new lead ligands.

Keywords: Click chemistry; FimH; Multivalency; Triazolyl α-d-mannosides.

MeSH terms

Cycloaddition Reaction
Hemagglutination*
Ligands
Mannosides*

Substances

Ligands
Mannosides