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.

三氟乙酸（TFA）是一种强酸，常用于从固相树脂中裂解合成的多肽，也可用于提高多肽纯化步骤中的HPLC性能。默认情况下，定制的多肽是以冻干的TFA盐的形式交付的，其中TFA的含量可能高达10-45%。

定制多肽中的TFA可能会导致后续检测数据出现无法解释的差异。例如，nM浓度的TFA已被证明会干扰细胞实验，在某些情况下会抑制细胞增殖，而在其他情况下会增加细胞活力。

TFA去除服务推荐用于:

• 将用于细胞试验的多肽
• 将被用作原料药或制成品的多肽
• 含有大量碱性残基的亲水多肽

干品多肽的重量中不仅仅包含多肽，还包含有一些非肽的组份，如水、被吸收的溶剂、配位离子和盐等。肽的净含量是指肽在其中的重量百分比，这个百分比的数值范围很大，可能从50%到90%，取决于纯度、序列以及合成和纯化的方法，不要将肽的净含量和肽的纯度混为一谈，他们是两个完全不同的概念。纯度通常是通过HPLC测定的。纯度定义的是多肽样品中含正确序列的组分的百分比，而肽的净含量是指样品中肽类物质相对于总物质所占的百分比，肽的净含量通常是氨基酸组分分析或紫外分光法测定的，这个信息主要是在一些对肽的浓度很敏感的实验中，对计算肽的浓度是很重要的。