小麦麸皮烷基间苯二酚抑制α-葡萄糖苷酶的构效关系研究  

Study on the structure-activity relationship of inhibition on α-glucosidase by wheat bran alkylresorcinols

作　　者：屠洁[1] 刘冠卉 曹喜涛[1] 赵静 李强[1] 季更生[1] TU Jie;LIU Guanhui;CAO Xitao;ZHAO Jing;LI Qiang;JI Gengsheng(School of Biotechnology,Jiangsu University of Science and Technology,Zhenjiang 212018,China;School of Grain Industry,Jiangsu University of Science and Technology,Zhenjiang 212018,China)

机构地区：[1]江苏科技大学生物技术学院,镇江212018 [2]江苏科技大学粮食学院,镇江212018

出　　处：《江苏科技大学学报（自然科学版）》2019年第6期93-98,共6页Journal of Jiangsu University of Science and Technology:Natural Science Edition

基　　金：江苏省镇江市重点研发计划(现代农业)项目(NY201620)

摘　　要：为了阐明两亲性酚类类脂烷基间苯二酚(alkyresorcinols,ARs)抑制α-葡萄糖苷酶的构效关系,以小麦麸皮ARs(C17∶0、C19∶0、C21∶0、C23∶0、C25∶0)为研究对象,测定其对α-葡萄糖苷酶活性的抑制,并利用分子对接及LogP值分析软件初步研究了抑制活性差异的可能机制.结果表明,随着烷基侧链的增长,ARs的LogP值逐渐增加,对α-葡萄糖苷酶活性的抑制呈先上升后下降的变化,其中ARs(C19∶0)的抑制活性最强,IC50值为66.17μmol/L.ARs(C17∶0)通过亲水头部进入酶分子活性区,通过苯环羟基和酶分子Glu422形成氢键,而ARs(C19∶0)则是以疏水性尾部进入酶分子活性区,通过苯环羟基、酶分子Glu422及His423形成氢键,同时还存在疏水性氨基酸和烷基侧链之间的疏水作用;ARs(C21∶0)与酶的作用类似于ARs(C19∶0),但是苯环羟基仅和酶分子Glu422形成氢键,烷基链与酶分子的疏水作用则增强;ARs(C23∶0)和ARs(C25∶0)均未能在酶分子活性区域完成分子的对接.由此可知,ARs分子亲水、亲脂基团的平衡是影响其与酶分子相互作用及抑制活性的重要因素.In order to elucidate the structure-activity relationship between amphipathic phenolic lipid alkylresorcinols(ARs)andα-glucosidase,the wheat bran ARs(C17∶0,C19∶0,C21∶0,C23∶0,C25∶0)were used to determine the inhibitory activities onα-glucosidase.The molecular docking and lipophilic parameter LogP were analyzed to preliminarily study the possible mechanism of the inhibition of ARs onα-glucosidase.The results showed that the LogP value increased with the growth of alkyl side chains,while the activities ofα-glucosidase increased first and then decreased.5-nonadecylresorcinol(C19:0)showed the most robust inhibition againstα-glucosidase,and the value of half inhibitory concentration(IC50)onα-glucosidase was 66.17μmol/L.Further investigation speculated that 5-hexadecylresorcinol(C17∶0)might entered the active region ofα-glucosidase by its hydrophilic head,and formed a hydrogen bond between the phenyl ring hydroxyl and Glu422 of the enzyme molecule,while 5-nonadecylresorcinol(C19∶0)entered the active region of the enzyme molecule by the hydrophobic tail,and hydrogen bonds were formed between the benzene ring hydroxy and enzyme molecules Glu422 and His423,and hydrophobic interactions between hydrophobic amino acids and alkyl chains were also present.The interaction between 5-heneicosylresorcinol(C21∶0)and the enzyme was similar to that of 5-nonadecylresorcinol(C19∶0).However,the phenyl ring hydroxyl only formed hydrogen bonds with the enzyme molecule Glu422,and the hydrophobic interaction between the alkyl chain and the enzyme molecule was enhanced.On the other hand,both 5-tricosylresorcinol(C23∶0)and 5-pentacosylresorcinol(C25∶0)failed to dock in the active region of the enzyme.In summary,the changes in the alkyl chain length of ARs leads the changes of balance between lipophilic and hydrophobic groups which affects the interaction with the enzyme molecule and its inhibitory activities onα-glucosidase.

关 键 词：小麦麸皮 烷基间苯二酚 抑制 Α-葡萄糖苷酶 构效关系 

分 类 号：TS201.2[轻工技术与工程—食品科学]