‘Naked ’ and Hydrated Conformers of the Conserved Core Pentasaccharide of N‑linked Glycoproteins and Its Building Blocks

*S Supporting Information ABSTRACT: N-glycosylation of eukaryotic proteins is wide-spread and vital to survival. The pentasaccharide unit −Man3GlcNAc2 − lies at the protein-junction core of all oligosaccharides attached to asparagine side chains during this process. Although its absolute conservation implies an indis-pensable role, associated perhaps with its structure, its unbiased conformation and the potential modulating role of solvation are unknown; both have now been explored through a combination of synthesis, laser spectroscopy, and computation. The proximal −GlcNAc-GlcNAc − unit acts as a rigid rod, while the central, and unusual, −Man-β-1,4-GlcNAc − linkage is more flexible and is modulated by the distal Man-α-1,3 − and Man-α-1,6 − branching units. Solvation stiffens the ‘rod ’ but leaves the distal residues flexible, through a β-Man pivot, ensuring anchored projection from the protein shell while allowing flexible interaction of the distal portion of N-glycosylation with bulk water and biomolecular assemblies