Neu5Acα2,6Galβ1,4GlcNAc

Neu5Acα2,6Galβ1,4GlcNAc (N-acetylneuraminic acid α2-6 linked to galactose β1-4 N-acetylglucosamine) is a core sialylated trisaccharide motif prevalent in human milk oligosaccharides (HMOs), glycoproteins, and glycolipids, recognized as the type-2 chain sialyl structure formed by ST6Gal-I sialyltransferase action on the lacNAc acceptor. This α2,6-sialylated disaccharide serves as a key building block for higher HMOs like LSTc (sialyllacto-N-tetraose c) and extended poly-N-acetyllactosamine chains, modulating protein glycosylation, pathogen binding, and immune recognition in the neonatal gut. Absent the nonhuman Neu5Gc, it features human-specific N-acetyl sialic acid, distinguishing it from α2,3/α2,6 Neu5Gc variants linked to xenosialylation and cancer. In HMOs, it acts as a decoy receptor for enteric pathogens (e.g., rotavirus, norovirus), promotes Bifidobacterium adhesion/prebiotic effects, and influences sialidase activity in microbiota. Synthetic/free forms are vital for glycan arrays, lectin studies, and therapeutics targeting Siglec receptors in autoimmunity/inflammation, with emerging roles in infant formula fortification for microbiome modulation and antiviral protection.

Appearance

• White to off-white lyophilized amorphous powder.
• Hygroscopic solid, often freeze-dried for purity.

Source

• Abundant in human/colostrum HMOs (~10-20% sialylated fraction).
• Enzymatic synthesis via ST6Gal1 on Galβ1,4GlcNAc; natural from milk/glycoproteins.

Molecular Weight and Structure

• Formula: C23H38N2O19; MW 634.55 g/mol (reducing trisaccharide).
• Neu5Acα2→6Galβ1→4GlcNAc (linear type-2 chain with axial α2,6 sialyl linkage).

Sugar Specificity

• Selective α2,6-sialyl motif for human Siglecs (e.g., Siglec-2/5), rotaviral VP4.
• Differs from α2,3 isomer by equatorial sialic acid orientation.

Biological Activity

• Prebiotic: Bifidogenic growth, pathogen adhesion blockade (e.g., E. coli F17).
• Immunomodulatory: Inhibits Siglec signaling, reduces neonatal inflammation.

Purity and Microbial Contamination

• ≥98% by HPLC/NMR for standards.
• Endotoxin <0.05 EU/mg; sterile, bioburden <5 CFU/g.

Identity and Quality Control

• 1H-NMR (anomeric shifts), HRMS (m/z 633 [M-H]-), sialidase linkage analysis.
• IP-RP-HPLC, monosaccharide profiling post-acid hydrolysis.

Shelf Life and Storage

• 3 years lyophilized at -20°C; solutions stable 1 month 4°C.
• Desiccated, avoid light/moisture/frequent freeze-thaws.

Applications

• HMO/infant formula ingredients; glycan microarray standards.
• Antiviral research, glycotherapy for Siglec-related diseases.

Key Characteristics

• Highly water-soluble (>200 mg/mL); stable human sialyl-type 2 ligand.
• Non-immunogenic, bifidogenic, anti-adhesive properties.

Citation Links

• https://pubchem.ncbi.nlm.nih.gov/compound/91862595
• https://pmc.ncbi.nlm.nih.gov/articles/PMC6753469/
• https://www.sciencedirect.com/science/article/pii/S2161831322010110
• https://pmc.ncbi.nlm.nih.gov/articles/PMC9304252/
• https://glyconnect.expasy.org/hmo/structures
• https://pubchem.ncbi.nlm.nih.gov/compound/121853
• https://pmc.ncbi.nlm.nih.gov/articles/PMC6724515/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC9237113/
• https://www.elicityl-oligotech.com/human-milk-oligosaccharides-hmo
• https://pubmed.ncbi.nlm.nih.gov/20946833/