将脱羧酶OleT JE和P450BM3的还原酶结构域融合,产生自给自足的蛋白OleT-BM3R,该蛋白能够在温和的水性条件下,以O 2为溶剂,有效催化羧酸氧化成线性α-烯烃(LAO)的氧化脱羧。氧化剂和NADPH作为电子供体。安装在融合蛋白中的兼容电子转移系统不仅消除了对辅助氧化还原伴侣的需求,而且还提高了脱羧反应性并扩大了底物范围。结合基于亚磷酸酯脱氢酶的NADPH再生系统,这种酶促反应的产物滴定度提高至2.51 g L –1,容积生产率达到209.2 mg L –1 h在低催化剂负载量(约0.02 mol%)下为–1。凭借其稳定性和可扩展性,这种自给自足的生物催化剂提供了一种自然友好的方法来递送LAO。
STAPLED TRIAZOLE CO-AGONISTS OF THE GLUCAGON AND GLP-1 RECEPTORS
申请人:MERCK SHARP & DOHME CORP.
公开号:EP3842061A1
公开(公告)日:2021-06-30
ABSTRACT OF THE DISCLOSURE
The stapled peptides of the present invention, and pharmaceutically acceptable salts thereof, are co-agonists of the glucagon and GLP-1 receptors, and may be useful in the treatment, prevention and suppression of diseases mediated by the glucagon receptor and the GLP-1 receptor, including but not limited to, metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.