Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance
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 xylopyra...
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MDPI AG
2025-07-01
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| Series: | Molecules |
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| author | Sven Ole Jaeschke Ingo vom Sondern Thisbe K. Lindhorst |
| author_facet | Sven Ole Jaeschke Ingo vom Sondern Thisbe K. Lindhorst |
| author_sort | Sven Ole Jaeschke |
| collection | DOAJ |
| description | 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 <sup>4</sup><i>C</i><sub>1</sub> and a <sup>1</sup><i>C</i><sub>4</sub> 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. |
| format | Article |
| id | doaj-art-21fe38f94c8d4e0a8a43ddbc99384405 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-21fe38f94c8d4e0a8a43ddbc993844052025-08-20T03:36:31ZengMDPI AGMolecules1420-30492025-07-013015307410.3390/molecules30153074Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand DistanceSven Ole Jaeschke0Ingo vom Sondern1Thisbe K. Lindhorst2Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, 24098 Kiel, GermanyOtto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, 24098 Kiel, GermanyOtto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, 24098 Kiel, GermanyFunctional 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 <sup>4</sup><i>C</i><sub>1</sub> and a <sup>1</sup><i>C</i><sub>4</sub> 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.https://www.mdpi.com/1420-3049/30/15/3074carbohydrate chemistrycarbohydrate recognitionconformational switchbacterial adhesionFimHlectin inhibitors |
| spellingShingle | Sven Ole Jaeschke Ingo vom Sondern Thisbe K. Lindhorst Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance Molecules carbohydrate chemistry carbohydrate recognition conformational switch bacterial adhesion FimH lectin inhibitors |
| title | Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance |
| title_full | Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance |
| title_fullStr | Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance |
| title_full_unstemmed | Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance |
| title_short | Bivalent Inhibitors of Mannose-Specific Bacterial Adhesion: A Xylose-Based Conformational Switch to Control Glycoligand Distance |
| title_sort | bivalent inhibitors of mannose specific bacterial adhesion a xylose based conformational switch to control glycoligand distance |
| topic | carbohydrate chemistry carbohydrate recognition conformational switch bacterial adhesion FimH lectin inhibitors |
| url | https://www.mdpi.com/1420-3049/30/15/3074 |
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