超高效液相色谱-质谱联用法监测人心房钠尿肽的化学合成

Monitoring chemical synthesis of human atrial natriuretic peptide by ultra high performance liquid chromatography-mass spectrometry analysis

多肽作为神经递质、激素、受体等参与和调节许多重要的生命过程。随着对多肽结构与功能认识的深入,化学合成多肽在生物医药、生命分析等领域显示了重要价值。人心房钠尿肽(ANP)是一种由28个氨基酸组成的多肽类激素,其含量和代谢异常与心血管疾病、癌症等密切相关。针对ANP重要的生理功能,该文开展了ANP化学合成及其过程的监测与优化,设计了集固相合成线性直链多肽和液相氧化成环为一体的策略。基于高效液相色谱的分离性能和多级质谱的结构鉴定能力,建立了超高效液相色谱-串联质谱(UHPLC-MS/MS)分析新方法,对固相合成产物进行了分离分析,并对液相氧化方法进行了筛选和优化,最终分离纯化得到了目标多肽,为人心房钠尿肽的高效化学合成及氧化成环反应提供借鉴。

Peptides participate in and regulate many important life processes as neurotransmitters,hormones and receptors.With detailed understanding of the structure and function of peptides,chemically synthesized peptides have shown great value in the fields of biomedicine and life analysis.Human atrial natriuretic peptide(ANP)is a polypeptide hormone consisting of 28 amino acids.The abnormalities in the content and metabolism of ANP are closely related to the diseases like cardiovascular diseases and cancer.In view of the important physiological functions of ANP,herein we monitored and optimized the chemical synthesis of ANP chemical synthesis.The strategy involved integrating solid phase synthesis of linear peptide chain and liquid phase oxidation.Based on the excellent separation performance of HPLC and the excellent qualitative ability of mass spectrometry(MS),a new method based on ultra high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)was established to monitor the synthesis reaction and to separate and purify the obtained products.This study provides a reference for the efficient chemical synthesis and oxidative ring formation of human atrial natriuretic peptide.