Carbajo Daniel, El-Faham Ayman, Royo Miriam, Albericio Fernando
CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, 08028 Barcelona, Spain.
Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Spanish National Research Council (CSIC), 08034 Barcelona, Spain.
ACS Omega. 2019 May 17;4(5):8674-8680. doi: 10.1021/acsomega.9b00974. eCollection 2019 May 31.
The number of peptide-based active pharmaceutical ingredients (APIs) has increased enormously in recent years. Furthermore, the emerging new peptide drug candidates are more complex and larger. For the industrial solid-phase synthesis of C-carboxylic acid peptides, the two main resins available, Wang and chlorotrityl chloride (CTC), have a number of drawbacks. In this context, resins that form an amide bond with the first amino acid are more robust than Wang and CTC resins. Here, we address the use of the backbone (BAL) resin for the synthesis of the peptide liraglutide. The BAL resin, in conjunction with the use of pseudoprolines to avoid aggregation, allows the stepwise solid-phase synthesis of this API in excellent purity and yield.
近年来，基于肽的活性药物成分（API）数量大幅增加。此外，新出现的肽类候选药物更加复杂、分子更大。对于C-羧酸肽的工业固相合成，现有的两种主要树脂，即王氏树脂和氯三苯甲基氯（CTC）树脂，存在许多缺点。在这种情况下，与第一个氨基酸形成酰胺键的树脂比王氏树脂和CTC树脂更稳定。在此，我们阐述了主链（BAL）树脂在合成肽类药物利拉鲁肽中的应用。BAL树脂与使用拟脯氨酸以避免聚集相结合，能够以优异的纯度和产率逐步进行该API的固相合成。
