KD-mxyl peptide

• Handling and Storage of Synthetic Peptides
• Material Safety Data Sheets (MSDS)

Batch to batch variation of the purity

The KD-mxyl peptide is a macrocyclic β-arch peptide designed to mimic core structural motifs observed in pathological tau filaments. This peptide features a di-Cys meta-xylyl staple that enforces a conformation resembling cross-β amyloid folds found in tau aggregates associated with neurodegenerative disorders. Structural characterization by cryo-EM reveals that KD-mxyl adopts a β-arch fold spanning residues I297-Y310, with two β-strands connected by a five-residue β-arc. The peptide self-assembles into amyloid filaments exhibiting cross-β architecture, as confirmed by X-ray fiber diffraction showing characteristic 4.8 Å and 11.0 Å reflections.

In cellular assays, KD-mxyl demonstrates potent seeding activity for endogenous tau aggregation, forming fluorescent puncta in engineered biosensor cells expressing tau-RD^LM-YFP. The seeding capacity is sequence-dependent and requires macrocyclic constraint, as scrambled or linear control peptides show significantly reduced activity. Cryo-EM structures of KD-mxyl filaments show remarkable conformational congruence with core folds from tau extracts obtained from individuals, especially those related to argyrophilic grain disease and corticobasal degeneration. The structural features include conserved side-chain interactions and β-sheet arrangements that recapitulate key elements of pathological tau filaments.

• Angera IJ, Xu X, Rajewski BH, Hallinan GI, Zhang X, Ghetti B, Vidal R, Jiang W, Del Valle JR. Macrocyclic β-arch peptides that mimic the structure and function of disease-associated tau folds. Nat Chem. 2025 Jun;17(6):865-874. doi: 10.1038/s41557-025-01805-z. Epub 2025 Apr 30. PMID: 40307419.

Trifluoroacetic acid (TFA) is a common counterion from the purification process using High-Performance Liquid Chromatography (HPLC). The presence of TFA can affect the peptide's net weight, appearance, and solubility.

Impact on Net Weight: The TFA salt contributes to the total mass of the product. In most cases, the peptide content constitutes >80% of the total weight, with TFA accounting for the remainder.

Solubility: TFA salts generally enhance the solubility of peptides in aqueous solutions.

In Biological Assays: For most standard in vitro assays, the residual TFA levels do not cause interference. However, for highly sensitive cellular or biochemical studies, please be aware of its presence.