Glucagon-like peptide-1 (GLP-1) is a potential therapeutic agent for treating Type 2 diabetes, owing to its glucose-dependent capability to stimulate insulin secretion. Semaglutide is currently the best GLP-1 analogue; however, the Aib8 -Arg34 -GLP-1 (7-37) of semaglutide contains an unnatural amino acid at the eighth position (Aib: 2-aminoisobutyric acid), which hinders its fermentation process. Aib8 -Arg34 -GLP-1 (7-37) is mainly synthesised by solid-phase synthesis. However, solid-phase synthesis of Aib8 -Arg34 -GLP-1 (7-37) has many shortcomings: (i) The synthesis requires many organic solvents, (ii) the existence of deletion peptides impedes the subsequent purification process, (iii) the yield is low (approximately 16%), and (iv) it is not suitable for large-scale synthesis. However, the synthesis of Aib8 -Arg34 -GLP-1 (7-37) by liquid-phase fragment condensation of expressed and synthetic peptides (Arg34 -GLP-1 (9-37) and Boc-His (Boc)-Aib) has many advantages: (i) The synthesis process only requires a few organic reagents, (ii) the yield is high (approximately 60%), (iii) the purification conditions are simple and Aib8 -Arg34 -GLP-1 (7-37) with a purity of over 98% is obtained through one-step reverse-phase purification, and (iv) the raw materials are inexpensive and large-scale synthesis is possible. In conclusion, here, we developed an efficient method for synthesising Aib8 -Arg34 -GLP-1 (7-37).

中文翻译：

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通过液相片段浓缩高效合成 Aib8 -Arg34 -GLP-1 (7-37)。

胰高血糖素样肽-1 (GLP-1) 是治疗 2 型糖尿病的潜在治疗剂，因为它具有刺激胰岛素分泌的葡萄糖依赖性能力。索马鲁肽是目前最好的 GLP-1 类似物；然而，semaglutide的Aib8 -Arg34 -GLP-1 (7-37)在第8位含有非天然氨基酸（Aib：2-氨基异丁酸），阻碍了其发酵过程。Aib8 -Arg34 -GLP-1 (7-37) 主要通过固相合成。然而，Aib8 -Arg34 -GLP-1 (7-37) 的固相合成有很多缺点：(i) 合成需要很多有机溶剂，(ii) 缺失肽的存在阻碍了后续的纯化过程，(iii)产率低（约 16%），并且（iv）不适合大规模合成。然而，通过表达和合成肽（Arg34 -GLP-1 (9-37) 和 Boc-His (Boc)-Aib）的液相片段缩合合成 Aib8 -Arg34 -GLP-1 (7-37) 具有许多优点: (i) 合成过程仅需少量有机试剂，(ii) 收率高（约 60%），(iii) 纯化条件简单，Aib8 -Arg34 -GLP-1 (7-37)一步反相提纯，纯度可达98％以上，原料便宜，可大规模合成。总之，在这里，我们开发了一种合成 Aib8 -Arg34 -GLP-1 (7-37) 的有效方法。(iii)纯化条件简单，通过一步反相纯化得到纯度在98%以上的Aib8-Arg34-GLP-1(7-37)，(iv)原料价廉物美规模合成是可能的。总之，在这里，我们开发了一种合成 Aib8 -Arg34 -GLP-1 (7-37) 的有效方法。(iii)纯化条件简单，通过一步反相纯化得到纯度在98%以上的Aib8-Arg34-GLP-1(7-37)，(iv)原料价廉物美规模合成是可能的。总之，在这里，我们开发了一种合成 Aib8 -Arg34 -GLP-1 (7-37) 的有效方法。