全國多肽合成技術_多肽合成技術_Peptide synthesis technology
訂書多肽合成技術
生物體內的多種生命進程調節都是通過蛋白質與蛋白質之間的相互作用來實現的。例如病毒的自組裝，細胞的生長，分裂，分化等過程。而通常蛋白-蛋白相互作用的界面太大，從而使小分子藥物很難對其進行靶向定位，達到高效特異性地阻斷這種相互作用，展現良好的治療效果。蛋白類藥物因為很難順利通過細胞膜所以也達不到直接靶向細胞內相互作用的效果，因此，研究者們開始尋求一種能夠克服這兩種藥物缺點的既能夠進入細胞膜又能特異性靶向蛋白-蛋白相互作用的新的藥物分子。
研究表明，具有α-螺旋結構和富含正電荷的多肽可以穿過細胞膜。但是一旦從母體分離就不能保持其原有的二級結構，構象的不穩定導致其與蛋白質的結合作用減弱，而普通的線性多肽不能穿過細胞膜且容易被水解。經過不斷嘗試，Verdine等發展了一種新型結構的多肽，這種多肽被稱為訂書肽，它是一種全碳支架的具有α-螺旋結構的多肽，全碳支架穩定α-螺旋結構，增強了多肽分子與蛋白質的相互作用，並且訂書肽能夠穿過細胞膜，不容易被水解，相比於之前的小分子藥物和蛋白類藥物，具有更高的藥理活性。
訂書肽的合成與普通多肽合成的區別在於在固相合成肽鏈過程中引入兩個含有α-甲基，α-烯基的非天然氨基酸，然後兩個非天然氨基酸之間發生烯烴複分解反應環化構成穩定α-螺旋結構構象的全碳支架，進而合成訂書肽。
上圖為兩種不同構型的含有α-甲基，α-烯基的非天然氨基酸的一般結構。這種類型的氨基酸合成方法一般為：
訂書肽的一般合成路線為：
國肽生物始終堅持客戶至上的經營理念，通過長久的實驗累積，不斷優化合成條件和純化工藝，已經具備了成熟的訂書肽合成工藝，具有了向全球提供高品質的訂書多肽的能力，能夠充分滿足客戶的各種研發需要。
成功案例：
合成下列結構訂書肽
HPLC分析：
MS分析：
合肥國肽生物官網：
翻譯：
translation:
Subsidiary peptide synthesis technology
The regulation of multiple life processes in an organism is achieved through the interaction between proteins and proteins. For example, self-assembly of viruses, cell growth, division, differentiation and the like. Usually, the interface of protein-protein interaction is too large, so that it is difficult for small molecule drugs to target them, and the interaction is effectively and specifically blocked, showing good therapeutic effects. Because protein drugs are difficult to pass through the cell membrane, they do not directly target intracellular interactions. Therefore, researchers have begun to seek a solution that can overcome the shortcomings of these two drugs and enter the cell membrane and specific targets. A new drug molecule that interacts with protein-proteins.
Studies have shown that polypeptides with alpha-helical structures and positively charged can cross cell membranes. However, once it is separated from the mother, its original secondary structure cannot be maintained. The instability of the conformation causes its binding to proteins to be weakened, while the ordinary linear polypeptide cannot pass through the cell membrane and is easily hydrolyzed. After repeated attempts, Verdine et al. developed a novel structure of a peptide called a staple peptide, which is an all-carbon scaffold with an α-helical structure and an all-carbon scaffold that stabilizes the α-helical structure. The interaction between the polypeptide molecule and the protein is enhanced, and the peptide can pass through the cell membrane and is not easily hydrolyzed, and has higher pharmacological activity than the previous small molecule drugs and protein drugs.
The synthesis of a peptide is different from the synthesis of a common polypeptide by introducing two unnatural amino acids containing an α-methyl group, an α-alkenyl group, and then an olefin metathesis reaction between two unnatural amino acids. Cyclization constitutes a full carbon scaffold that stabilizes the conformation of the α-helical structure, thereby synthesizing the book peptide.
The top panel shows the general structure of an unnatural amino acid containing alpha-methyl, alpha-alkenyl groups in two different configurations. This type of amino acid synthesis is generally:
The general synthetic route for a peptide is:
National Peptide Biotechnology always adheres to the customer-oriented business philosophy. Through long-term experimental accumulation, continuous optimization of synthesis conditions and purification processes, it has a mature synthesis process of peptides, and has the ability to provide high-quality peptides to the world. Can fully meet the various research and development needs of customers.
success case:
Synthesis of the following structural peptides
HPLC analysis:
MS analysis:
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