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肥胖代谢综合征治疗新靶点——神经肽Y衍生物的设计与合成及测定分析 被引量:1

Design,Synthesis and Analysis of Human Neuropeptide Y Derivative
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摘要 目的为了探索人神经肽Y(hNPY)与老年人肥胖及其代谢综合征之间的相关关系、新的发病机制以及其在老年临床医学治疗的新靶点,我们进行了hNPY衍生物——聚乙二醇化神经肽Y(mPEG4-hNPY)的设计与合成,同时对合成的mPEG4-hNPY进行测定分析,以确定合成此多肽的纯度和分子量等。方法mPEG4-hNPY合成采用化学固相合成法,纯度测定采用高效液相色谱法(HPLC),其分子量测定采用电喷雾离子化质谱法(ESI—IT-MS)。结果采用HPLC检测化学固相法合成的mPEG4-hNPY的纯度为96.29%;采用ESI检测出3H+-7H+5个目标峰的mPEG4-hNPY,分子量范围在4532.0~4534.2Da,该分子量与其理论值4534.0Da高度吻合,且小于允许误差范围0.1%。它们的质荷比分别为:[M+3H]3H+质荷比为1512.4m/z,实测分子量为4534.2Da;[M+4H]4H+质荷比为1134.2m/z,实测分子量为4532.8Da;[M+5H]5H+质荷比为907.4in/z,实测分子量为4532.0Da;[M+6H]6H+质荷比为756.4m/z,实测分子量为4532.4Da;[M+7H]7H+质荷比为648.6m/z,实测分子量为4533.2Da。结论采用化学固相合成法可成功合成mPEG4-hNPY,这为今后进行人体肥胖代谢综合征临床发病的分子机制研究,以及未来老年医学临床采用新靶点治疗与干预等提供了科学依据和物质基础。 Objective To design, synthesize and analyze PEGylated human neuropeptide Y (mPEG4 - hNPY), derivative of hNPY, which is a new target for the treatment of human obesity metabolic syndrome. Methods Chemical solid phase synthesis was adopted for synthesis of mPEG4 -hNPY. High performance liquid chromatography (HPLC) was applied for purity determination. Electrospay ionization ion trap mass spectrometry (ESI -IT -MS) was employed for molecular weight measurement. Results HPLC analysis showed that the purity of mPEG4 - hNPY produced by chemical solid phase synthesis reached 96. 29%. ESI demonstrated five target peaks of mPEG4 - hNPY between 3 H+ and 7H +. The molecular weight ranged between 4532. 0 to 4534.2 Dalton,which was highly consistent with theoretical value of 4534. 0 Dalton. The mass charge ratio and measured molecular weight were 1512.4 m/z and 4534. 2 Dalton at [M +3H] 3H+ , 1134.2 m/z and 4532. 8 Dalton at [M +4H] 4H+ , 907.4 m/z and 4532.0 Dalton at [M+5H] 5H+, 756. 4 m/z and 4532. 4 Dalton at [M+6H] 6H +, 648.6m/z and 4533.2 Dalton at [M+7H] 7H+, respectively. Conclusion mPEG4 -hNPY can be successfully synthesized by chemical solid phase synthesis.
作者 滕肇慧 杨永鹏 董萍 丁宇 王媛媛 丁克祥 Teng Zhaohui;Yang Yongpeng;Dong Ping;Ding Yu;Wang Yuanyuan;Ding Kexiang(Dalian Beverly Cosmetic Hospital,Dalian 116000,China;Southern Hospital,Southern Medical University,Guangzhou 510515,China;School of Public Health,Southern Medical University,Guangzhou 510515,China)
出处 《国际老年医学杂志》 2018年第5期205-210,237,共7页 International Journal of Geriatrics
基金 马中课题合作電点攻关项目(MCLS20170329AMC-SMU06)
关键词 肥胖代谢综合征 聚乙二醇化神经肽Y 多肽合成 Obesity metabolic syndrome PEGylated human neuropeptide Y Polypeptide synthesis
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