Sperling Oliver, Fuchs Andreas, Lindhorst Thisbe K
Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 4, 24098, Kiel, Germany.
Org Biomol Chem. 2006 Nov 7;4(21):3913-22. doi: 10.1039/b610745a. Epub 2006 Sep 25.
Fimbriae are proteinogeneous appendages on the surface of bacteria, which mediate bacterial adhesion to the host cell glycocalyx. The so-called type 1 fimbriae exhibit specificity for alpha-d-mannosides and, therefore, they are assumed to mediate bacterial adhesion via the interaction of a fimbrial lectin and alpha-d-mannosyl residues exposed on the host cell surface. This carbohydrate-specific adhesive protein subunit of type 1 fimbriae has been identified as a protein called FimH. The crystal structure of this lectin is known and, based on this information, the molecular details of the interaction of mannoside ligands and FimH are addressed in this paper. Computer-based docking methods were used to evaluate known ligands as well as to design new ones. Then, a series of new mannosides with extended aglycon was synthesized and tested as inhibitors of type 1 fimbriae-mediated bacterial adhesion in an ELISA. The results obtained were compared to the predictions and findings as delivered by molecular modeling. This study led to an improved understanding of the ligand-receptor interactions under investigation.
菌毛是细菌表面的蛋白质附属物，介导细菌与宿主细胞糖萼的黏附。所谓的1型菌毛对α - d - 甘露糖苷具有特异性，因此，推测它们通过菌毛凝集素与宿主细胞表面暴露的α - d - 甘露糖基残基之间的相互作用来介导细菌黏附。1型菌毛这种碳水化合物特异性黏附蛋白亚基已被鉴定为一种名为FimH的蛋白质。该凝集素的晶体结构已知，基于此信息，本文探讨了甘露糖苷配体与FimH相互作用的分子细节。使用基于计算机的对接方法来评估已知配体并设计新的配体。然后，合成了一系列具有延长苷元的新甘露糖苷，并在酶联免疫吸附测定（ELISA）中作为1型菌毛介导的细菌黏附抑制剂进行测试。将获得的结果与分子建模的预测和发现进行比较。这项研究有助于更好地理解所研究的配体 - 受体相互作用。
