Jaeschke Sven Ole, Vom Sondern Ingo, Lindhorst Thisbe K
Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, 24098 Kiel, Germany.
Molecules. 2025 Jul 23;30(15):3074. doi: 10.3390/molecules30153074.
Functional glycomimetics is suited to study the parameters of carbohydrate recognition that forms the basis of glycobiology. It is particularly attractive when a glycoligand allows for the investigation of two different states, such as varying distance between multiple glycoligands. Here, a xylopyranoside was employed as a scaffold for the presentation of two mannoside units which are ligands of the bacterial lectin FimH. The chair conformation of the central xyloside can be switched between a and a conformation whereby the two conjugated mannoside ligands are flipped from a di-equatorial into a di-axial position. Concomitantly, the distance between the two glycoligands changes and, as a consequence, so does the biological activity of the respective bivalent glycocluster, as shown in adhesion-inhibition assays with live bacteria. Molecular modeling was employed to correlate the inter-ligand distance with the structure of the formed glycocluster-FimH complex. Our study suggests that conformational switches can be employed and further advanced as smart molecular tools to study structural boundary conditions of carbohydrate recognition in a bottom-up approach.
功能性糖模拟物适用于研究构成糖生物学基础的碳水化合物识别参数。当一种糖配体能够研究两种不同状态时，它就特别有吸引力，比如多个糖配体之间不同的距离。在这里，吡喃木糖苷被用作展示两个甘露糖苷单元的支架，这两个甘露糖苷单元是细菌凝集素FimH的配体。中心木糖苷的椅式构象可以在α和β构象之间切换，由此两个共轭甘露糖苷配体从二平伏键位置翻转到二直立键位置。同时，两个糖配体之间的距离发生变化，相应地，各自二价糖簇的生物活性也会改变，如在与活细菌的黏附抑制试验中所示。采用分子建模将配体间距离与形成的糖簇 - FimH复合物的结构相关联。我们的研究表明，构象转换可以作为智能分子工具被采用并进一步发展，以自下而上的方式研究碳水化合物识别的结构边界条件。
