环糊精与苦味寡肽的超分子结构自组装与作用机制研究

In the duration to produce bioactive peptides, the generation of bitter oligopeptides usually brings about serious adverse impacts. Theoretical and experimental investigations have shown bitter taste of bitter oligopeptides can be significantly influenced by their hydrophobicity. Due to the characteristics of cyclodextrin (CD) with a hydrophilic exterior and a hydrophobic cavity, we propose CDs might be used to reduce or even exterminate bitter taste of such peptides. However, to date, ability and mechanism of CDs to remove bitter taste of bitter oligopeptides have not been entirely determined. We will employ experimental and computational approaches, involving supramolecular generation, electronic taste recognition, wave spectrum and structural analysis, molecular structure-activity relationship and modeling, molecular dynamics and quantum chemistry simulation, etc., to explore self-assembled and interaction mechanisms of supramolecular structures of CDs with oligopeptides, and demonstrate how several key factors, including amino acid composition, chiral and structural features of oligopeptides, and environmental conditions, affect the interactions of bitter oligopeptides with CDs and their derivatives. We also will set up quantitative prediction and evaluation methodology of bitter oligopeptides mediated by CDs. This project is of theoretical and practical significance for understanding the interaction mechanisms of CDs with bitter oligopeptides, as well as adopting CD-based methods to eliminate bitter taste of bitter oligopeptides and other unfavorable taste. What’s more, this project can serve as important methodological references for investigations on CDs interacting with peptides or proteins in the field of food, biology and chemistry, etc.

在生物活性肽制备过程中，苦味寡肽的产生常导致非常不利的影响。前期的理论与实验证明，疏水性对于寡肽的苦味具有重要影响。环糊精(CD)具有内疏水、外亲水特征，因此，采取CD掩盖或降低寡肽的苦味成为可能。但CD改善寡肽苦味的特征与机理并未得到完全澄清。本课题将整合实验与计算策略，包括超分子复合、电子味觉识别、波谱与结构解析、分子构效与建模、分子动力学与量子化学模拟等，阐释寡肽的氨基酸组成、手性与结构特征、环境条件等因素对CD(包括衍生物)-苦味寡肽超分子结构自组装与作用的影响机制，并建立CD介导的苦味寡肽定量构效预测与评价方法。课题的实施对CD-苦味寡肽作用机制的深入理解及采用CD包埋法去除生物活性寡肽的苦味或其它异源味具有重要的理论与实践意义，同时，也可为食品、生物与化学等领域中CD与多肽或蛋白的相互作用研究提供重要的方法学借鉴。

在生物活性肽制备过程中，苦味寡肽的产生常常导致非常不利的影响。前期的理论与实验证明，疏水性对于寡肽的苦味具有重要影响。环糊精(CD)具有内疏水、外亲水特征，因此，采取CD掩盖或降低寡肽的苦味成为可能。但CD介导寡肽苦味的特征与机理并未得到完全澄清。本课题整合实验与计算策略，包括超分子组装、电子味觉识别、波谱与结构解析、分子构效与建模、量子化学计算等，阐释了寡肽的氨基酸组成、手性与结构特征、环境条件等因素对各种不同CD-苦味寡肽超分子结构自组装与作用的影响机制，并建立了CD介导的苦味寡肽定量结构-苦味预测与评价方法。具体包括：. (1)环糊精去除苦味寡肽的苦味特征评价：通过电子舌结合感官评价方法评价环糊精去除寡肽苦味的效果。(2)环糊精与疏水氨基酸的作用特征研究：采用NMR、荧光光谱、圆二色谱、TEM、UV、IR、DSC、分子对接、量子化学计算等研究了各种环糊精与疏水氨基酸的作用机制。(3)环糊精与苦味寡肽的作用特征研究：采用NMR、荧光光谱、圆二色谱、TEM、UV、IR、DSC、分子对接、量子化学计算等研究了各种环糊精与苦味寡肽的作用机制。(4)环糊精介导的苦味寡肽定量结构-苦味关系预测方法的建立：重点研究了肽的结构表征与建模技术，进而建立了苦味寡肽的定量结构-苦味关系预测与评价方法。. 本基金资助下，目前已发表SCI论文11篇，已申请国家发明专利1项，先后有4位博士和4位硕士参与本项目研究。课题的实施对CD-苦味寡肽作用机制的深入理解及采用CD包埋法去除或者掩盖生物活性寡肽的苦味或其它异源味具有重要的理论与实践意义，同时，也可为食品、生物与化学等领域中CD与多肽或活性分子的相互作用研究提供重要的方法学借鉴。