High-mannose-type N-glycan (HMG)

High-mannose-type N-glycans are essential carbohydrate structures added to asparagine residues of proteins during early-stage post-translational modification in the endoplasmic reticulum. They typically consist of a core of two N-acetylglucosamines and five to nine mannose residues (Man5-Man9), joined by specific alpha-1,2, alpha-1,3, and alpha-1,6 glycosidic linkages. While these structures are normally processed into complex or hybrid glycans in the Golgi apparatus, they are often retained at high densities on the surfaces of certain viruses, such as HIV-1 and SARS-CoV-2, forming a 'glycan shield' that protects vulnerable protein epitopes from the host immune system. In oncology, an increased abundance of high-mannose glycans on the cell surface is associated with malignant transformation and serves as a biomarker for tumor progression and metastasis. Therapeutic strategies involve the use of broadly neutralizing antibodies (bNAbs) or carbohydrate-binding lectins to block viral entry or deliver cytotoxic payloads directly to high-mannose-expressing cancer cells. However, high-mannose content on therapeutic monoclonal antibodies can lead to significantly faster systemic clearance via the hepatic mannose receptor, posing a challenge for maintaining drug half-life.

Other names

High-mannose linkagesOligomannose N-glycansHigh-mannose oligosaccharidesMannose-rich glycansHigh-mannose-type N-linked glycansMannose patch

Neutralization of viral entry by binding to the glycan shield and occluding receptor binding sites; induction of antibody-dependent cellular cytotoxicity (ADCC) against infected or malignant cells; targeted delivery of toxins via lectin-drug conjugates (LDCs) [2][4][14].