最新發表論文
Modular Click Assembly of Trivalent Scaffolds Displaying Homogeneous and Mixed Human Milk Oligosaccharide Motifs

Human milk oligosaccharides (HMOs) modulate infant-microbe and immune interactions, yet broader structure-function understanding is limited by low abundance, isomeric complexity, and difficulty controlling multivalent presentation. We introduce a glycomimetic platform that assembles trivalent HMO displays from a tri-alkyne core via copper-catalyzed azide-alkyne cycloaddition. Azido-functionalized HMOs, including lacto-N-neofucopentaose I, lacto-N-fucopentaose I, lacto-N-fucopentaose V, and lacto-N-triose II, are installed to give mono-, di-, or tri-substituted conjugates in a single step; combining mono- and di-substituted intermediates furnishes heterovalent (mixed-display) constructs. Substitution patterns reveal motif-dependent steric effects that cap trisubstitution, consistent with largely independent reactivity of the three alkyne sites. The workflow offers orthogonal control over display density, motif composition, and interglycan distance, enabling homogeneous or mixed presentations from simple building blocks. This scalable approach delivers well-defined multivalent HMO architectures to enable presentation-dependent comparisons in glycan-protein recognition and to facilitate structure-function exploration beyond native scaffolds.