Department of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Shandong Women's University, Jinan 250300, China.
J Med Chem. 2024 Mar 14;67(5):3232-3243. doi: 10.1021/acs.jmedchem.3c02055. Epub 2024 Mar 5.
The molecular origin of the sweet taste is still elusive. Herein, the canonical AH-B-X theory of sweet taste is extended by resurveying various sweeteners, which provides deeper insights into an analogous intramolecular connectivity pattern of both glucophores in sweeteners and their interaction counterparts in sweet taste receptor TAS1R2/TAS1R3: electrostatic complementarity and topochemical compatibility. Furthermore, their complementary interaction is elaborately illustrated, accounting for the common molecular feature of eliciting sweetness. Moreover, it highlights that multiple glucophores in a topological system synergistically mediate the elicitation and performance of sweetness. This perspective presents a meaningful framework for the structure-activity relationship-based molecular design and modification of sweeteners and sheds light on the mechanism of molecular evolution of TAS1R2s/TAS1R3s. The link between palatability of sweeteners and harmony relationships between their structural components via stereochemistry and network has significant implications to illuminate the underlying mechanisms by which nature designs chemical reactions to elicit the most important taste.
甜味的分子起源仍然难以捉摸。在此，通过重新研究各种甜味剂，扩展了甜味的经典 AH-B-X 理论，从而深入了解了甜味剂中糖基和甜味受体 TAS1R2/TAS1R3 中其相互作用对应物的类似分子内连接模式：静电互补和拓扑化学兼容性。此外，还详细说明了它们的互补相互作用，解释了引起甜味的共同分子特征。此外，它还强调了拓扑系统中的多个糖基协同调节甜味的引发和表现。这种观点为基于结构-活性关系的甜味剂分子设计和修饰提供了有意义的框架，并揭示了 TAS1R2s/TAS1R3s 分子进化的机制。甜味剂的可接受性与其结构成分之间通过立体化学和网络的协调性之间的联系，对于阐明大自然设计化学反应以引起最重要的味道的潜在机制具有重要意义。
