一种筛选血管紧张素转换酶抑制肽的方法

实验建立一种从蛋白水解物中快速高效鉴别血管紧张素转化酶抑制剂(ACEI)的方法：先对蛋白按照酶解位点进行序列搜寻,建立一个样品肽库;在量效结构关系(QSAR)研究的基础上对样品库中的肽的ACE抑制活性进行预测,然后化学合成目标肽及测定活性;必要时用现代分析技术确证蛋白水解物中目标肽的存在。用此方法对油菜、大米、小麦蛋白水解物中三肽ACE抑制活性进行研究,发现IC50在10μmol/L以下的三肽多达34条,选择了11条活性较高的肽合成验证,最后发现潜藏在油菜Cruciferin BNC1 (P33523)蛋白序列347～349的LRL活性最高,IC50达到3.42μmol/L,且具有较好的稳定性。抑制动力学研究表明,LRL属于竞争性抑制剂;油菜蛋白胃蛋白酶水解物进行分子质量分段,取分子质量小于1000D部分进行高效液相色谱(HPLC)分析发现有LRL。     

Modelling relationship between angiotensin-(I)-converting enzyme inhibition and the bitter taste of peptides

Relationships between angiotensin-(I)-converting enzyme inhibition and the bitter taste of peptides were studied. In cases where ACE inhibition or bitter taste had not been experimentally determined, their activity was estimated using several different peptide quantitative structure–activity relationship (QSAR) models. Significant correlations between increased ACE inhibition and bitterness were found for dipeptides using both observed and QSAR-predicted values. The relationship between ACE inhibition and bitter taste was attributed to the importance of hydrophobicity for both properties. Limited structural variations for dipeptides could make it difficult to have features that limit the effect of C-terminal hydrophobicity, necessary for ACE inhibition, on bitter taste. A similar modelling approach was also done on data from observed bitter oligopeptides derived from milk proteins. The relationship between QSAR-predicted ACE inhibition and observed bitter taste was not as strong as that found for dipeptides. Larger structural variation possibilities for oligopeptides than for dipeptides may thus make it, more feasible to find a highly efficient ACE inhibitory oligopeptide with a negligible bitter taste than a dipeptide.     

Adsorption and Quantum Chemical Studies on the Inhibition Potentials of Some Thiosemicarbazides for the Corrosion of Mild Steel in Acidic Medium

Three thiosemicarbazides, namely 2-(2-aminophenyl)-N phenylhydrazinecarbothioamide (AP4PT), N,2-diphenylhydrazinecarbothioamide (D4PT) and 2-(2-hydroxyphenyl)-N-phenyl hydrazinecarbothioamide (HP4PT), were investigated as corrosion inhibitors for mild steel in H₂SO₄ solution using gravimetric and gasometric methods. The results revealed that they all inhibit corrosion and their % inhibition efficiencies (%IE) follow the order: AP4PT > HP4PT > D4PT. The %IE obtained from the gravimetric and gasometric experiments were in good agreement. The thermodynamic parameters obtained support a physical adsorption mechanism and the adsorption followed the Langmuir adsorption isotherm. Some quantum chemical parameters were calculated using different methods and correlated with the experimental %IE. Quantitative structure activity relationship (QSAR) approach was used on a composite index of some quantum chemical parameters to characterize the inhibition performance of the studied molecules. The results showed that the %IE were closely related to some of the quantum chemical parameters, but with varying degrees. The calculated/theoretical %IE of the molecules were found to be close to their experimental %IE. The local reactivity has been studied through the Fukui and condensed softness indices in order to predict both the reactive centers and to know the possible sites of nucleophilic and electrophilic attacks.     

4-(1-哌嗪)类香豆素化合物体外抗血小板凝结活性的QSAR模型研究

采用Chem3D软件自带的分子力学MM2模块对17种4-(1-哌嗪)类香豆素化合物进行几何结构预优化。通过DFT中B3LYP方法在6-31G(d,p)基组水平上对其进行几何构型的全优化。提取Gaussian以及HyperChem软件中相关的量子化学参数并进行相关分析以及回归分析,构建了最优的QSAR模型:lg(1/IC50)=-104.3(±35.203)×ELUMO-0.003(±0.001)EHF-25.549(±7.278),n=11,R=0.821,R2=0.674,R2(cv)=0.593,σ=0.257,F=18.028。     

5′-甲硫腺苷核苷酶抑制剂的QSAR研究

通过构建33个甲硫腺苷(MTA)类似物的化学结构模型,并使用Molconn-Z统计的电子拓扑指数、形状指数和分子连接性指数作为受试化合物分子结构参数,结合多元线性回归(MLR)方法对MTA类似物的抑制活性进行了QSAR研究。所得模型的R和R2adj分别为0.862和0.711,表明该模型具有较好的预测和反映真实情况的能力。模型表明,MTA类似物的抑制活性与其所含硫和氮原子的电子拓扑指数以及分子形状指数相关,这为预测其他类似物的活性和设计新的抑制剂提供了理论依据。     

拓扑指数估算氯苯胺类化合物对发光细菌毒性

基于化学拓扑理论, 计算了14 种氯代苯胺衍生物的电拓扑状态指数(E_n)、连接指数(^mX ^v_p)。用多元回归研究了这些化合物的发光细菌急性毒性(-lgEC50)与E_n , ^mX ^v_p 的定量关系。经逐步回归分析, 建立了最佳的定量结构-生物活性相关(QSAR)模型, 相关系数为0 .979 。用Jackknife 法检验具有良好的稳健性与预测能力, 其计算值与实验值基本吻合。     

分子电性-距离矢量对典型抗HIV类药物的有效表征

采用二维拓扑结构描述子—分子电性距离矢量(MEDV),对TIBO类衍生物、非核苷类逆转录酶抑制剂和环脲类化合物等三类抗HIV病毒的药物定量结构活性关系进行了研究.用MEDV描述子对三类药物分子进行结构表征,以VSMP法对所得的91个分子结构描述符进行优化筛选以得到最优子集,用多元线性回归方法(MLR)分别构建了三类抗HIV病毒药分子结构与生物活性之间的定量构效关系(QSAR)模型.模型相关系数r分别为0.930 4,0.852 5和0.957 9,留一法交互验证(leave-one-out cross validation,LOO-CV)相关系数q分别为0.888 8,0.815 5和0.908 4,表明QSAR模型具有良好的稳定性和预测能力.QSAR模型表明分子中取代基团的种类和取代位置对药物分子的生物活性有显著影响.     

3，7一二氯-8-喹啉羧酸酯类化合物QSAR方程的建立

为了寻找活性更高和作用更温和的除草剂,研究了3,7－二氯－8－喹啉羧酸衍生物的结构与活性的关系;对其14种酯进行了合成,并测定了这14种酯的生理活性;用Hansch分析方法建立了这类化合物生物活性的定量构效关系方程,这一方程表明此类化合物的生物活性与取代基长度参数L、MR和取代基的宽度参数B1、B2和B4呈线性关系。     

三唑基香豆素荧光性能的构效关系研究

采用分子力学MM2对15种三唑基香豆素化合物进行结构预优化。在B3LYP/6-31G(d,p)基组水平上对三唑基香豆素化合物进行构型全优化。通过线性回归分析建立了最优构效关系模型,获得了对三唑基香豆素化合物的荧光性能(Φ)影响较大的结构参数。结果表明,三唑环电荷(QTRIA)和分子表面积(S)是影响三唑基香豆素化合物荧光量子产生率最主要的两个原因,荧光量子产生率与QTRIA呈正相关,与S呈负相关。所得到的QSAR方程对该系列化合物的荧光量子产生率有较好的预测效果。