Acetylated Trivalent Mannobioses: Chemical Modification, Structural Elucidation, and Biological Evaluation. (22nd February 2016)

• Record Type: Journal Article
• Authors: Rahkila, Jani; Panchadhayee, Rajib; Ardá, Ana; Jiménez‐Barbero, Jesús; Savolainen, Johannes; Leino, Reko
• Is Part Of: ChemMedChem. Volume 11:Number 6(2016)
• Page Start: 562
• Page End: 574
• Publication Date: 2016-02-22
• Subjects: carbohydrates -- glycoclusters -- immunostimulation -- molecular modeling -- NMR spectroscopy; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600076
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: People suffering from allergies can be treated with repeated injections of increasing amounts of a specific allergen. This type of specific immunotherapy is currently the only way to treat the underlying pathological immune response associated with an allergy. The approach can afford long‐lasting protection, but the process takes 3–5 years, can produce allergic reactions, and in severe cases treatment is often aborted due to anaphylaxis. However, treatment can be optimized with the use of specific adjuvants that modify the immune response, its duration, and that increase the production of the correct type of antibodies. In the pursuit of such adjuvants, two new trivalent acetylated β‐(1→2)‐linked mannobioses based on a previously discovered lead molecule were prepared. The new molecules, along with the previously developed lead, were investigated by rigorous NMR and molecular modeling experiments in order to elucidate their behavior and preferred conformations in solution. Furthermore, the molecules were subjected to a biological investigation in which their immunostimulatory properties were evaluated by assessing their effect on the production of TH 2‐type cytokine interleukin‐4 (IL‐4) and Treg pro‐inflammatory cytokine tumor necrosis factor (TNF). Treatment of peripheral mononuclear blood cell cultures from patients suffering from birch allergy with birch allergen Bet v induced a strong IL‐4 response, whereas the same treatment together with the trivalent acetylated mannobioses caused significant suppression of the induced IL‐4. Abstract : Nothing to sneeze at : Two new acetylated trivalent β‐(1→2)‐linked mannobioses were synthesized and screened for biological activity as immunostimulatory adjuvants for potential use in the treatment of severe allergy sufferers. These two compounds, along with another previously prepared analogue, were subjected to meticulous NMR and molecular modeling studies to determine their behavior in solution.