Lacto-N-neotetraose

Lacto-N-neotetraose (LNnT)

Lacto-N-neotetraose is a type of human milk oligosaccharide (HMO) classified as a tetrasaccharide, consisting of four monosaccharide units linked in a specific structural sequence. It is a type II chain HMO, distinguished from its structural isomer lacto-N-tetraose (LNT) by the glycosidic linkage of the terminal galactose.

• Abbreviation: LNnT
• IUPAC Abbreviation: Gal-β1,4-GlcNAc-β1,3-Gal-β1,4-Glc
• Molecular Formula: C26H45NO21
• Molecular Mass: 707.63 g/mol
• CAS Number: 13007-32-4

Chemical and Structural Description

LNnT consists of a lactose core (galactose-β1,4-glucose) extended by an N-acetyllactosamine unit (galactose-β1,4-N-acetylglucosamine). This makes it a type II chain oligosaccharide where the terminal galactose is β1,4-linked to N-acetylglucosamine—unlike LNT, which has a β1,3 linkage. LNnT is a structural isomer of LNT, with biological properties influenced by the change in glycosidic linkage. It appears as a white to off-white hygroscopic powder, soluble in water, and should be stored under cool, dry conditions to prevent degradation. It is a reducing sugar that exists in equilibrium between α and β anomers at the reducing end.

Biological and Functional Context

LNnT is naturally present in human milk, typically at concentrations of 0.2–0.6 g/L, and is one of the most abundant HMOs in some individuals depending on maternal secretor status. It selectively stimulates growth of beneficial gut bacteria, particularly Bifidobacterium longum subsp. infantis and Bifidobacterium breve, modulates immune responses, supports mucosal immunity, and prevents pathogen binding (e.g., Campylobacter jejuni and certain E. coli) to intestinal epithelial cells. Due to these functions, LNnT is added to infant formulas and functional foods to mimic the benefits of breastfeeding.

Analytical Confirmation and Production

Its structure is confirmed via high-resolution NMR spectroscopy, mass spectrometry (MS), and high-performance liquid chromatography (HPLC). For commercial use, LNnT is typically produced via enzymatic biosynthesis or microbial fermentation with genetically engineered microorganisms, as extracting it from human milk is impractical for large-scale production.

Specification Table

Related Compounds

Lacto-N-tetraose (LNT) – Type I chain isomer with β1,3 linkage instead of β1,4. Lacto-N-fucopentaose I/II/III (LNFP I/II/III) – Fucosylated derivatives of LNT or LNnT with additional immune functions. N-acetyllactosamine (LacNAc) – Disaccharide unit present in LNnT.

Lacto-N-neotetraose (LNnT) is a naturally occurring type II HMO that promotes healthy gut microbiota, supports immune development, and inhibits pathogen colonization in infants. Its structural difference from LNT influences its functional properties, making it an important addition in infant formula supplementation and medical nutrition products.