
- 序列:YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS (X2 and X13 are α-amino isobutyric acid (Aib), S39 is L-serinamide, and K20 is N6-{N-(hydrogen icosanedioyl)-γ-Glu-bis[iminobis(ethylenoxy)acetyl]}-Lysine)
- 分子式:C225H348N48O68
- 分子量:4813.45
相关文档
批次之间数据可能略有差异
相关文档
批次之间数据可能略有差异
Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clinical outcomes beyond those achieved by a selective GLP-1 receptor agonist. Tirzepatide was discovered by engineering GLP-1 activity into the GIP sequence. It is an imbalanced dual agonist in favor of GIPR over GLP-1R activity as the molecule shows equal affinity for the GIPR compared with native GIP but binds the GLP-1R with approximately 5-fold weaker affinity than native GLP-1. The imbalanced nature of tirzepatide may be critical to maximizing the efficacy of a dual agonist because dose escalation for GLP-1R activation can be limited by gastrointestinal effects such as nausea and vomiting, while GIPR engagement is not known to be associated with similar events. As a consequence, a pharmacological profile favoring potency at the GIPR offers an opportunity to fully engage this pathway while minimizing GLP-1–related tolerability issues. In addition to a potency ratio toward GIPR activity, tirzepatide contains a C20 unsaturated di-acid acyl chain to affect albumin binding, and the overall properties of the molecule enable once-weekly dosing. Beyond convenience, this pharmacokinetic feature may confer pharmacodynamic benefit, as high and sustained concentrations of selective GLP-1R agonists have enhanced clinical efficacy.
Notes:
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:
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。
多肽合成服务: 纽普生物(NovoPro)提供常规多肽合成、糖修饰多肽合成、稳定同位素标记的多肽合成、磷酸化多肽合成、荧光标记多肽、多肽的BSA/KLH/OVA等载体蛋白的偶联等服务