在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,...在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,在调节生物活性方面具有很大的前景。本文重点介绍MGs在药物开发领域的应用,包括蛋白质–蛋白质相互作用(PPI)稳定性和蛋白质降解。我们深入分析了各种MGs的结构以及MGs与各种生物活性分子之间的相互作用,从而为PPI稳定剂和新型降解剂的开发提供了新的视角。Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.展开更多
由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强...由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强度的概念对蚁群聚类算法中的拾起/放下规则加以改进,以连接强度作为拾起规则,对结点进行聚类,并根据放下规则放弃部分不良数据,产生最终聚类结果.最后采用了MIPS数据库中的PPI数据进行实验,将JSACO算法与PPI网络数据的其他聚类算法进行比较,聚类结果表明JSACO算法正确率高,时间开销低.展开更多
文摘在过去的二十年里,随着IMiD和indisulam等MG降解剂的出现,分子胶(MGs)逐渐引起了制药界的关注。这些分子通过促进靶蛋白和E3连接酶之间的相互作用来降解靶蛋白。此外,MGs作为化学诱导剂,促进同源蛋白和异源蛋白的二聚化形成三元复合物,在调节生物活性方面具有很大的前景。本文重点介绍MGs在药物开发领域的应用,包括蛋白质–蛋白质相互作用(PPI)稳定性和蛋白质降解。我们深入分析了各种MGs的结构以及MGs与各种生物活性分子之间的相互作用,从而为PPI稳定剂和新型降解剂的开发提供了新的视角。Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.
文摘由于PPI网络数据的无尺度和小世界特性,使得目前对此类数据的聚类算法效果不理想.根据PPI网络的拓扑结构特性,本文提出了一种基于连接强度的蚁群优化(Joint Strength based Ant Colony Optimization,JSACO)聚类算法,该算法引入了连接强度的概念对蚁群聚类算法中的拾起/放下规则加以改进,以连接强度作为拾起规则,对结点进行聚类,并根据放下规则放弃部分不良数据,产生最终聚类结果.最后采用了MIPS数据库中的PPI数据进行实验,将JSACO算法与PPI网络数据的其他聚类算法进行比较,聚类结果表明JSACO算法正确率高,时间开销低.
