Ser(OGlcNAc)]400-KWK-Tau (388-411)-KK(Biotin)-NH2

Product Name: Ser(OGlcNAc)]400-KWK-Tau (388-411)-KK(Biotin)-NH2

Sequence One Letter Code: KWKHGAEIVYKSPVV-S(OGlcNAc)-GDTSPRHLSNVK-K(biotin)-NH2

Sequence Three Letter Code: Lys-Trp-Lys-His-Gly-Ala-Glu-Ile-Val-Tyr-Lys-Ser-Pro-Val-Val-Ser((OGlcNAc) - Gly-Asp-Thr-Ser-Pro-Arg-His-Leu-Ser-Asn-Val-Lys- Lys(biotin) - NH2

Molecular Weight: 3677.5

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Alzheimer's Disease

Source / Species: human

Conjugation: Conjugated

Conjugation Type: Biotins

Code Nacres: NA.26

Application: Ser(O-GlcNAc)400–Tau (388–411)-KK(Biotin)-NH₂ is a synthetic tau peptide encompassing residues 388–411 and modified with O-linked N-acetylglucosamine at serine 400, a modification identified in rat brain. Tau undergoes extensive post-translational modification, and O-GlcNAcylation is thought to modulate phosphorylation patterns and aggregation propensity in Alzheimer’s disease. The C-terminal biotin tag facilitates affinity capture and protein interaction studies. This peptide is used to investigate crosstalk between O-GlcNAcylation and phosphorylation, tau aggregation mechanisms, and signaling pathways implicated in neurodegeneration. It supports biochemical, proteomic, and mechanistic studies of tau pathology.

Current Research: Ser(O-GlcNAc)400–Tau (388–411)-KK(Biotin)-NH₂ is a synthetic peptide derived from residues 388–411 of human tau and site-specifically modified with O-linked N-acetylglucosamine (O-GlcNAc) at serine 400. A C-terminal KK-biotin tag enables affinity-based applications, and amidation enhances stability and structural mimicry of the native backbone. This region lies within the C-terminal portion of tau, adjacent to the microtubule-binding repeat domains that are central to aggregation and filament formation in Alzheimer’s disease (AD) and related tauopathies. Tau is extensively post-translationally modified, with phosphorylation being the most studied alteration in neurodegeneration. However, O-GlcNAcylation—addition of a single N-acetylglucosamine moiety to serine or threonine residues by O-GlcNAc transferase (OGT)—has emerged as a critical regulatory modification. Unlike complex glycosylation in the secretory pathway, O-GlcNAcylation is a dynamic, cytoplasmic and nuclear modification that responds to cellular metabolic state via the hexosamine biosynthetic pathway. O-GlcNAcase (OGA) reverses this modification, creating a tightly regulated cycle analogous to phosphorylation–dephosphorylation dynamics. Current research emphasizes reciprocal crosstalk between O-GlcNAcylation and phosphorylation on tau. Numerous studies demonstrate that increased O-GlcNAcylation correlates with reduced tau hyperphosphorylation, a hallmark of AD pathology. Mechanistically, O-GlcNAc at specific residues may sterically hinder kinase access, alter local conformation, or modulate protein–protein interactions that influence kinase or phosphatase recruitment. Ser400 is among the sites identified as O-GlcNAc–modified in brain tissue, and modification at this position may influence phosphorylation at nearby residues within the C-terminal region. The Tau (388–411) segment includes sequences adjacent to the microtubule-binding repeats and regions implicated in aggregation and conformational transitions. Modifications in this domain may affect tau’s propensity to self-associate or form β-sheet–rich fibrillar assemblies. Synthetic peptides bearing O-GlcNAc at Ser400 enable controlled in vitro studies to determine how this modification alters aggregation kinetics, oligomer formation, and fibril morphology. Techniques such as thioflavin T fluorescence, circular dichroism, and electron microscopy are commonly employed to evaluate structural effects. The C-terminal KK(Biotin) tag facilitates immobilization on streptavidin-coated matrices for pull-down assays and proteomic profiling. This configuration allows identification of proteins that selectively bind O-GlcNAc–modified versus unmodified tau sequences. Such studies help define O-GlcNAc “reader” interactions or assess recruitment of kinases, phosphatases, chaperones, or aggregation modulators. Comparative binding analyses clarify whether O-GlcNAc at Ser400 promotes or inhibits association with regulatory complexes. In enzymology research, the peptide serves as a substrate for examining OGT and OGA specificity. It can also be used to assess how adjacent phosphorylation influences O-GlcNAc cycling, providing insight into modification hierarchy and site competition. Given that impaired glucose metabolism and reduced global O-GlcNAcylation are observed in AD brains, understanding site-specific regulation at residues such as Ser400 has translational relevance. Therapeutic research increasingly explores OGA inhibitors to elevate tau O-GlcNAcylation and reduce pathological phosphorylation and aggregation. Defined peptides like Ser(O-GlcNAc)400–Tau (388–411) provide molecular tools to validate antibody specificity, map modification-dependent interactions, and evaluate pharmacologic modulation of O-GlcNAc dynamics. Overall, Ser(O-GlcNAc)400–Tau (388–411)-KK(Biotin)-NH₂ is a precisely engineered reagent for dissecting the interplay between O-GlcNAcylation and phosphorylation in tau biology. By enabling controlled biochemical and proteomic analyses, it supports mechanistic studies of tau aggregation, metabolic regulation of post-translational modifications, and pathways contributing to neurodegenerative disease progression.