Phenylbutazone, a New Long‐Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier
Phenylbutazone, a New Long‐Acting Agent that can Improve the Peptide Pharmacokinetic Based on Serum Albumin as a Drug Carrier
复制标题
DOI：
10.1111/cbdd.12726
复制
发表时间：
2016-02
影响因子：
3
通讯作者：
Jie Zhou;Xue Li;Xiao-yun Zhu;Jian Sun;Qianqian Qiu;Wen-long Huang;Hai Qian
中科院分区：
文献类型：
--
作者：
Jie Zhou;Xue Li;Xiao-yun Zhu;Jian Sun;Qianqian Qiu;Wen-long Huang;Hai Qian
PYY 24 -36-Leu 31作为一种神经肽Y-2受体激动剂，据报道具有抑制食欲的作用，在肥胖治疗中具有潜力，但其半衰期短限制了临床应用。使用化学修饰来改善与人血清白蛋白（HSA）的相互作用是延长肽类似物半衰期的有效策略。因此，基于保泰松与人血清白蛋白结合良好的特点，我们选择了合适的接头与PYY 24 -36-Leu 31连接，构建了长效、高生物活性的PYY 24 -36-Leu 31偶联物，并成功找到了一种新型长效PYY 24 -36-Leu 31偶联物8，其在饮食中隔日给药诱导肥胖（DIO）小鼠2周，导致摄食量和体重显著降低，血液参数和肝脂肪变性改善。
As a NPY‐2 receptor agonist, PYY24–36‐Leu31 is reported to suppress appetite and has a potential in obesity treatment, but its short half‐life limits the clinical application. The use of chemical modification to improve interactions with human serum albumin (HSA) is an effective strategy for prolonging the half‐lives of peptide analogues. So based on the characteristics that phenylbutazone has a good combination with HSA, we selected a proper linker to link with PYY24–36‐Leu31 to create long‐acting and highly biologically active PYY24–36‐Leu31 conjugates, and successfully find a novel, long‐acting PYY24–36‐Leu31 conjugate 8 that, when dosed every other day in diet induce obese (DIO) mice for 2 weeks, results in a significant reduction in food intake and body weight and improvement in blood parameter and hepatic steatosis.