highmmannose

High-mannose, or oligomannose, refers to a class of N-linked glycans in which the glycan attached to an asparagine residue consists primarily of mannose units on a common chitobiose core. The core structures include two N-acetylglucosamine (GlcNAc) residues linked to the protein and a conserved trimannose core of three mannose units. High-mannose glycans extend this core by adding additional mannose residues, yielding compositions from Man5GlcNAc2 up to Man9GlcNAc2. These glycans are characterized by their relative simplicity and the predominance of mannose on the outer branches, with little or no elaboration by other sugars such as galactose or sialic acid.

Biosynthesis and maturation follow the early secretory pathway. N-glycosylation begins in the endoplasmic reticulum with the en bloc transfer of Glc3Man9GlcNAc2 to nascent proteins. Glucosidases I and II remove glucose residues to enable proper folding via the calnexin/calreticulin cycle. ER mannosidases can trim the glycan to Man5GlcNAc2, which may be retained for quality control or exported to the Golgi. In the Golgi, processing by additional mannosidases and glycosyltransferases typically produces hybrid or complex glycans; however, incomplete processing or selective retention can preserve high-mannose forms.

Occurrence and significance: High-mannose glycans are common on many glycoproteins synthesized in the ER, including certain viral envelope glycoproteins where processing is limited. They are recognized by mannose-binding lectins and can influence protein folding, trafficking, stability, and immune recognition. In biotechnology, the proportion of high-mannose glycans on therapeutic glycoproteins can affect pharmacokinetics and effector functions.

Analytical notes: Methods such as mass spectrometry, high-performance liquid chromatography, and lectin-based assays are used to characterize and distinguish high-mannose from hybrid and complex N-glycans.