Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering i...Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering its binding interaction in particular with cyclodextrins. NSAIDs are marketed as racemates, chiral discrimination and knowledge of enantiomeric bioavailability is essential. Circular dichroism (CD) spectroscopy is the technique of choice for elucidating chirality and monitoring and characterizing molecular recognition phenomena in solution. Methods em-ploying the fundamentals of the simultaneous measurements of absorbance and CD and a novel efficient titration method have been developed to study the binding of β-Cyclodextrin (β-CyD) and the two enantiomers of 2-PPA as a function of pH. The effect on physicochemical properties and bioavailability was investigated. The binding constant, stoichiometry and pKa for both the free and the bound drugs were determined using a Levenburg-Marquadt non-linear equation. The exact nature of the enantiomer discriminating interactions by cyclodextrins (CyDs) is not well understood. In this work, the interactions and co-conformations of both enantiomers of 2-PPA with β-CyD were explained and es-timated using spectroscopic variations upon complexation. The results indicated a change in the physicochemical prop-erties of 2-PPAs upon complexation and highlighted the enantioselective binding of β-CyD as a function of pH. The charge on the vip molecule and its stereochemistry are of great importance in regulating the stability of the vip/β-CyD complexes;hence the bioavailability of drugs. This work elucidates 2-PPAs/β-CyD binding interactions and highlights the effect of β-CyD on drugs with an effective novel method for binding titration and the potential of the simultaneous measurements of absorbance and CD in future chiral drug interactions studies.展开更多
芝麻是八大类食物过敏原之一,快速准确识别芝麻过敏原对预防其过敏有重要意义。核酸适配体可以高效识别靶标过敏原,在过敏原检测中有良好的应用前景。为了获得芝麻主要过敏原Ses i 2的特异性核酸适体,本研究以Ses i 2为靶标,通过磁珠筛...芝麻是八大类食物过敏原之一,快速准确识别芝麻过敏原对预防其过敏有重要意义。核酸适配体可以高效识别靶标过敏原,在过敏原检测中有良好的应用前景。为了获得芝麻主要过敏原Ses i 2的特异性核酸适体,本研究以Ses i 2为靶标,通过磁珠筛选法(磁珠-SELEX)开展10轮筛选,经由高通量测序获得6条候补序列(S1~S6),并进行家族性、同源性分析及二级结构预测。结果表明,6条候选核酸适体的重复率可达46.38%,其自由能在-9.02到-2.47 kcal·moL^(-1)之间,根据自由能能量稳定原则,S1和S5吉布斯自由能最低最稳定,分别为-6.70和-9.02 kcal·moL^(-1)。利用ELISA试验进行亲和力测试,结果表明核酸适体S1和S2的亲和能力较强,S1:KD=67.02 nmol·L^(-1),R2=0.925 8,S2:KD=97.65 nmol·L^(-1),R2=0.795 1。核酸适体S1与过敏原Ses i 2的结合力和其他过敏原蛋白相比有显著差异,可视为具有特异性。本研究最终获得一条兼具良好亲和力和特异性的核酸适体S1,为芝麻过敏原快速检测提供了技术支撑。展开更多
目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉...目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉正性重构的关系。方法按照住院先后顺序选取2022年1月至2023年6月河南科技大学第一附属医院心血管内科收治的老年CHD合并T2DM患者120例,根据重构指数分为正性重构组47例和非正性重构组73例。比较2组临床资料;采用多因素logistic回归分析冠状动脉正性重构的危险因素;采用Spearman相关性分析TyG和AIP与冠状动脉正性重构的相关性;采用ROC曲线分析TyG和AIP对冠状动脉正性重构的预测价值。结果正性重构组吸烟、三酰甘油、糖化血红蛋白、TyG、AIP显著高于非正性重构组,高密度脂蛋白胆固醇、血钙水平显著低于非正性重构组(P<0.05,P<0.01)。单因素logistic回归分析显示,吸烟、三酰甘油、高密度脂蛋白胆固醇、糖化血红蛋白、血钙、TyG、AIP是老年CHD合并T2DM患者冠状动脉正性重构的危险因素(P<0.05,P<0.01)。多因素logistic回归分析显示,TyG(OR=7.253,95%CI:2.458~13.364,P=0.035)、AIP(OR=6.017,95%CI:2.205~12.025,P=0.030)是老年CHD合并T2DM患者冠状动脉正性重构的独立危险因素(P<0.05)。TyG、AIP预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积分别为0.783、0.766,联合预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积为0.868,显著优于单独预测(P<0.05)。结论TyG和AIP与老年CHD合并T2DM患者冠状动脉正性重构密切相关,可作为预测冠状动脉正性重构的有效指标,对临床早期识别高危患者及制定个体化干预策略具有重要意义。展开更多
文摘Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering its binding interaction in particular with cyclodextrins. NSAIDs are marketed as racemates, chiral discrimination and knowledge of enantiomeric bioavailability is essential. Circular dichroism (CD) spectroscopy is the technique of choice for elucidating chirality and monitoring and characterizing molecular recognition phenomena in solution. Methods em-ploying the fundamentals of the simultaneous measurements of absorbance and CD and a novel efficient titration method have been developed to study the binding of β-Cyclodextrin (β-CyD) and the two enantiomers of 2-PPA as a function of pH. The effect on physicochemical properties and bioavailability was investigated. The binding constant, stoichiometry and pKa for both the free and the bound drugs were determined using a Levenburg-Marquadt non-linear equation. The exact nature of the enantiomer discriminating interactions by cyclodextrins (CyDs) is not well understood. In this work, the interactions and co-conformations of both enantiomers of 2-PPA with β-CyD were explained and es-timated using spectroscopic variations upon complexation. The results indicated a change in the physicochemical prop-erties of 2-PPAs upon complexation and highlighted the enantioselective binding of β-CyD as a function of pH. The charge on the vip molecule and its stereochemistry are of great importance in regulating the stability of the vip/β-CyD complexes;hence the bioavailability of drugs. This work elucidates 2-PPAs/β-CyD binding interactions and highlights the effect of β-CyD on drugs with an effective novel method for binding titration and the potential of the simultaneous measurements of absorbance and CD in future chiral drug interactions studies.
文摘芝麻是八大类食物过敏原之一,快速准确识别芝麻过敏原对预防其过敏有重要意义。核酸适配体可以高效识别靶标过敏原,在过敏原检测中有良好的应用前景。为了获得芝麻主要过敏原Ses i 2的特异性核酸适体,本研究以Ses i 2为靶标,通过磁珠筛选法(磁珠-SELEX)开展10轮筛选,经由高通量测序获得6条候补序列(S1~S6),并进行家族性、同源性分析及二级结构预测。结果表明,6条候选核酸适体的重复率可达46.38%,其自由能在-9.02到-2.47 kcal·moL^(-1)之间,根据自由能能量稳定原则,S1和S5吉布斯自由能最低最稳定,分别为-6.70和-9.02 kcal·moL^(-1)。利用ELISA试验进行亲和力测试,结果表明核酸适体S1和S2的亲和能力较强,S1:KD=67.02 nmol·L^(-1),R2=0.925 8,S2:KD=97.65 nmol·L^(-1),R2=0.795 1。核酸适体S1与过敏原Ses i 2的结合力和其他过敏原蛋白相比有显著差异,可视为具有特异性。本研究最终获得一条兼具良好亲和力和特异性的核酸适体S1,为芝麻过敏原快速检测提供了技术支撑。
文摘目的探讨三酰甘油葡萄糖乘积(triglyceride-glucose index,TyG)指数和血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)与老年冠心病(coronary heart disease,CHD)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者冠状动脉正性重构的关系。方法按照住院先后顺序选取2022年1月至2023年6月河南科技大学第一附属医院心血管内科收治的老年CHD合并T2DM患者120例,根据重构指数分为正性重构组47例和非正性重构组73例。比较2组临床资料;采用多因素logistic回归分析冠状动脉正性重构的危险因素;采用Spearman相关性分析TyG和AIP与冠状动脉正性重构的相关性;采用ROC曲线分析TyG和AIP对冠状动脉正性重构的预测价值。结果正性重构组吸烟、三酰甘油、糖化血红蛋白、TyG、AIP显著高于非正性重构组,高密度脂蛋白胆固醇、血钙水平显著低于非正性重构组(P<0.05,P<0.01)。单因素logistic回归分析显示,吸烟、三酰甘油、高密度脂蛋白胆固醇、糖化血红蛋白、血钙、TyG、AIP是老年CHD合并T2DM患者冠状动脉正性重构的危险因素(P<0.05,P<0.01)。多因素logistic回归分析显示,TyG(OR=7.253,95%CI:2.458~13.364,P=0.035)、AIP(OR=6.017,95%CI:2.205~12.025,P=0.030)是老年CHD合并T2DM患者冠状动脉正性重构的独立危险因素(P<0.05)。TyG、AIP预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积分别为0.783、0.766,联合预测老年CHD合并T2DM患者冠状动脉正性重构的曲线下面积为0.868,显著优于单独预测(P<0.05)。结论TyG和AIP与老年CHD合并T2DM患者冠状动脉正性重构密切相关,可作为预测冠状动脉正性重构的有效指标,对临床早期识别高危患者及制定个体化干预策略具有重要意义。
