High-mannose-type glycan (HMG)

High-mannose-type glycans are a fundamental class of N-linked oligosaccharides consisting of two N-acetylglucosamine residues and a variable number of mannose residues, typically ranging from five to nine (Varki et al., 2015). These glycans are synthesized in the endoplasmic reticulum (ER) and serve as critical signals for protein folding and quality control via the calnexin/calreticulin cycle (Hebert et al., 2014). While usually processed into complex glycans in the Golgi apparatus of healthy cells, high-mannose structures are frequently retained on the surface of viral envelope proteins, such as HIV-1 gp120 and the SARS-CoV-2 spike protein, forming a "glycan shield" that facilitates immune evasion (Doores, 2015). In oncology, aberrant overexpression of high-mannose glycans is a hallmark of several cancers, including breast and colorectal cancer, making them valuable biomarkers and therapeutic targets (Maki et al., 2020). Drugs targeting these glycans, including carbohydrate-binding agents like Griffithsin and broadly neutralizing antibodies like 2G12, aim to inhibit viral entry or selectively eliminate malignant cells (Balzarini, 2007).

Other names

Oligomannose-type glycanHigh-mannose N-glycanMan5-9GlcNAc2High-mannose oligosaccharide

Binding to the high-mannose patch on viral envelope glycoproteins (e.g., gp120) to sterically hinder receptor binding and prevent viral entry; recognition of aberrant high-mannose clusters on tumor cells to trigger immune-mediated clearance (Balzarini, 2007; Doores, 2015).