{"title":"底物引导的树脂结合氨基酸新型直接酰胺化反应","authors":"Hiroki Ozasa, H. Mikamiyama, Hisashi Yamamoto","doi":"10.1093/chemle/upae107","DOIUrl":null,"url":null,"abstract":"\n In peptide drug discovery, the C-terminal structure of peptide compounds is crucial for enhancing the affinity with target proteins and for optimizing the compound's dynamics and physical properties. In conventional solid-phase synthesis, two steps are necessary to modify the C-terminal structure: cleavage from the resin and subsequent amidation involving activation of the resulting carboxylic acid. This process can potentially lead to racemization of the C-terminal amino acid side chain. To address this issue, we developed a novel method that, in the presence of a Ta catalyst, directly allows amines to react with amino acid-loaded resins, thereby accomplishing both resin cleavage and amidation in a single step.","PeriodicalId":9862,"journal":{"name":"Chemistry Letters","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Substrate-directed novel direct amidation of resin-bound amino acids\",\"authors\":\"Hiroki Ozasa, H. Mikamiyama, Hisashi Yamamoto\",\"doi\":\"10.1093/chemle/upae107\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n In peptide drug discovery, the C-terminal structure of peptide compounds is crucial for enhancing the affinity with target proteins and for optimizing the compound's dynamics and physical properties. In conventional solid-phase synthesis, two steps are necessary to modify the C-terminal structure: cleavage from the resin and subsequent amidation involving activation of the resulting carboxylic acid. This process can potentially lead to racemization of the C-terminal amino acid side chain. To address this issue, we developed a novel method that, in the presence of a Ta catalyst, directly allows amines to react with amino acid-loaded resins, thereby accomplishing both resin cleavage and amidation in a single step.\",\"PeriodicalId\":9862,\"journal\":{\"name\":\"Chemistry Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemistry Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1093/chemle/upae107\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1093/chemle/upae107","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
在多肽药物研发中,多肽化合物的 C 端结构对于提高与目标蛋白质的亲和力以及优化化合物的动力学和物理性质至关重要。在传统的固相合成过程中,需要两个步骤来改变 C 端结构:从树脂中裂解,然后对产生的羧酸进行活化酰胺化。这一过程有可能导致 C 端氨基酸侧链的消旋化。为了解决这个问题,我们开发了一种新方法,在 Ta 催化剂的作用下,直接让胺与负载氨基酸的树脂发生反应,从而一步完成树脂裂解和酰胺化。
Substrate-directed novel direct amidation of resin-bound amino acids
In peptide drug discovery, the C-terminal structure of peptide compounds is crucial for enhancing the affinity with target proteins and for optimizing the compound's dynamics and physical properties. In conventional solid-phase synthesis, two steps are necessary to modify the C-terminal structure: cleavage from the resin and subsequent amidation involving activation of the resulting carboxylic acid. This process can potentially lead to racemization of the C-terminal amino acid side chain. To address this issue, we developed a novel method that, in the presence of a Ta catalyst, directly allows amines to react with amino acid-loaded resins, thereby accomplishing both resin cleavage and amidation in a single step.