在固相合成上,發展一個可普遍應用且成功的??合成法,並且是以氮連接到固相載體,偶合的方法是形成活化的N-hydroxysuccinimide ester與氨基酸鋰鹽反應.這方法是試了不同的偶合試劑所得到的,且??合成後用TFA/CH2Cl2來將產物從固相載體上斷裂下來.而且用此方法合成不同的??組成的醯氨及酯類. 目前已經有許多抑制PTKs的藥物被研究,但關於PTPs的抑制劑非常少,而PTPs的多樣性使得這是藥物研究上值得開發的地方,而CD45是PTPs的一種主要為活化T細胞及B細胞,且對於自動免疫或慢性發炎的疾病,可以對CD45來著手,而天然物Pulchellalactam對CD45有抑制效果,我們發展一系列合成法可控制立體結構並且可任意更換不同取代基.以便尋找更有藥效的藥物 A general and successful N-terminal attachment methodology is described that allows the solid phase synthesis of oligopeptides from activated N-hydroxysuccinimide esters and amino acid lithium salts. The results of studies with different coupling systems for amide bond formation are presented. The oligomers were synthesized on solid support using a carbamate linker with final TFA/CH2Cl2 cleavage. This methodology was also applies for the preparation of peptide-substituted amides and esters in high purities and excellent yields. Numerous and specific inhibitors of PTKs have been discovered and tested as therapeutic agents against human disease. Currently, there are few readily available potent inhibitor of CD45 protein tyrosin phosphatase. CD45, has been shown to play crucial roles in activation of B and T cells. CD45 therefore represents a terapeutic target for various auto-immune and chronic anti-inflammatory diseases. We have completed the synthesis of Pulchellalactam, and we can change two different functional group for searching the best inhibitor.
