Enhanced Interfacial H‑Bond Networks Promote Glycan–Glycan Recognition and Interaction

H-bond networks at heterogeneous
interfaces play crucial
roles
in bioseparation, biocatalysis, biochip array profiling, and functional
nanosystem self-assembly, but their precise modulation and enhancement
remain challenging. In this study, we have discovered that interfacial
hydrophobic hydration significantly enhances H-bond networks at the
interface between a glycan-modified adsorbent and a methanol–water–acetonitrile
ternary solution. The enhanced H-bond networks greatly promote the
adsorbent–solution heterogeneous glycan–glycan recognition
and interaction. This novel hydrophobic hydration-enhanced hydrophilic
interaction (HEHI) strategy improves the affinity and efficiency of
intact glycopeptide enrichment. Compared with the commonly used hydrophilic-interaction
enrichment strategy, 23.5 and 48.5% more intact N- and O-glycopeptides are identified, and the enrichment
recoveries of half of the glycopeptides are increased >100%. Further,
in-depth profiling of both N- and O-glycosylation occurring on SARS-CoV-2 S1 and hACE2 proteins has
been achieved with more glycan types and novel O-glycosylation
information involved. Interfacial hydrophobic hydration provides a
powerful tool for the modulation of hydrophilic interactions in biological
systems.