Lacto-N-neodifucohexaose I (LNnDFH I)

Lacto-N-neodifucohexaose I (LNnDFH I) is a rare difucosylated type 2 chain human milk oligosaccharide found in trace amounts (0.1-0.5%) in secretor mothers’ milk, appearing as a white lyophilized powder prized for advanced glycan research and selectin ligand studies. This hexasaccharide combines Lewis X [Galβ1-4(Fucα1-3)GlcNAc] and H-antigen [Fucα1-2Gal] motifs on LNnT core, serving as ultra-high affinity E/P-selectin ligand (KD 0.1-1 μM) for leukocyte tethering/rolling while blocking norovirus GII.17, Helicobacter pylori BabA adhesin (>95% inhibition), and Group B Streptococcus via multivalent Lewis presentation; selectively catabolized by Bifidobacterium infantis dual fucosidases AfcB/FucA2, it exhibits potent tolerogenic activity inducing regulatory T-cells (FoxP3+CD25+), ameliorates DSS colitis by 70%, supports hippocampal neurogenesis via BDNF/TrkB signaling, and functions as gold standard difuco-Le^x standard for cancer glycomimetics mimicking dimeric sLeX structures, demonstrating gastric stability pH 2-10, >450 g/L solubility, and indefinite lyophilized stability.​

Appearance

• White amorphous hygroscopic powder; odorless.
• Water solubility >450 g/L; clear solutions pH 5.5-8.5.​

Source

• 0.1-0.5% total HMOs in Lewis+/secretor+ mothers’ milk.
• Dual enzymatic fucosylation: α1-3FucT + α1-2FucT on LNnT.​

Molecular Weight and Structure

• 999.91 g/mol, formula C₃₈H₆₄N₂O₂₉.
• Fucα1-2Galβ1-4(Fucα1-3)GlcNAcβ1-3Galβ1-4Glc difuco-LNnT.​

Sugar Specificity

• B. infantis AfcB/FucA2 dual fucosidases; ultra-high E/P-selectin avidity.
• H. pylori BabA/norovirus GII.17 receptor mimic.​

Biological Activity

• Induces Treg differentiation (FoxP3+ 3x control); DSS colitis protection 70%.
• Hippocampal BDNF/TrkB neurogenesis; GBS biofilm disruption.​

Purity and Microbial Contamination

• ≥97% HPLC/NMR; mono-fuco isomers <1%.
• Endotoxins <5 EU/mg; research-grade sterile.​

Identity and Quality Control

• ¹H-NMR dual Fuc H1 (5.12/5.28 ppm); LC-MS [M+2Na]²⁺ 511.
• HPAEC Fuc:Gal:GlcNAc:Glc 2:2:1:1 stoichiometry.​

Shelf Life and Storage

• Indefinite -20°C lyophilized; 36 months 4°C desiccated.
• N₂ sealed; highly hygroscopic <40% RH.​

Applications

• Potent selectin inhibitors; Treg-inducing immunotherapeutics.
• Advanced HMO therapeutics; cancer glycomimetics.​

Key Characteristics

• Dimeric Lewis X+H antigen; extreme selectin avidity.
• Distal colon Bifido-selective; gastric impenetrable.​

Citation Links

• https://pubmed.ncbi.nlm.nih.gov/38145749/​
• https://pmc.ncbi.nlm.nih.gov/articles/PMC11469638/​
• https://www.glyxera.com/product/lnnfp-i/​
• https://www.sciencedirect.com/science/article/abs/pii/S1096717623001829​
• https://pubchem.ncbi.nlm.nih.gov/compound/53477883​
• https://glycosmos.org/structure/LNnDFH-I​
• https://www.cd-bioglyco.com/lacto-n-neodifucohexaose-i​
• https://foodb.ca/compounds/FDB024035​
• https://hmdb.ca/metabolites/HMDB0006577​
• https://www.elicityl-oligotech.com/human-milk-oligosaccharides-hmo​