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) has a significant impact on peptides due to its role in the peptide synthesis process.

TFA is essential for the protonation of peptides that lack basic amino acids such as Arginine (Arg), Histidine (His), and Lysine (Lys), or ones that have blocked N-termini. As a result, peptides often contain TFA salts in the final product.

TFA residues, when present in custom peptides, can cause unpredictable fluctuations in experimental data. At a nanomolar (nM) level, TFA can influence cell experiments, hindering cell growth at low concentrations (as low as 10 nM) and promoting it at higher doses (0.5–7.0 mM). It can also serve as an allosteric regulator on the GlyR of glycine receptors, thereby increasing receptor activity at lower glycine concentrations.

In an in vivo setting, TFA can trifluoroacetylate amino groups in proteins and phospholipids, inducing potentially unwanted antibody responses. Moreover, TFA can impact structure studies as it affects spectrum absorption.