التفاصيل البيبلوغرافية
| العنوان: |
Dynamic Chirality in the Mechanism of Action of Allosteric CD36 Modulators of Macrophage-Driven Inflammation |
| المؤلفون: |
Danelius, Emma, Ohm, Ragnhild G., Ahsanullah, Mulumba, Mukandila, Ong, Huy, Chemtob, Sylvain, Erdelyi, Mate, 1975, Lubell, William D. |
| المصدر: |
Journal of Medicinal Chemistry. 62:11071-11079 |
| مصطلحات موضوعية: |
Chemical Sciences, Kemi |
| الوصف: |
© 2019 American Chemical Society. Dynamic chirality influences numerous processes in nature from protein folding to catalysis. Azapeptides are peptidomimetics possessing semicarbazide residues that can interconvert between sp2 and sp3 hybridization, resulting in stereodynamic interconversions of pseudo-R and -S-configurations by means of a planar intermediate. Cyclic azapeptides have shown unprecedented binding affinity to the cluster of differentiation 36 receptor (CD36) and ability to mitigate macrophage-driven inflammation by modulation of the toll-like receptor 2/6 pathway. A novel approach to synthesize cyclic peptides via A3-macrocyclization has been used to make R- and S-configuration controls to study the relevance of semicarbazide hybridization for modulator activity. Nuclear magnetic resonance spectroscopy analysis of potent cyclic azapeptide CD36 modulators (e.g., 1 and 2) and related cyclic peptides demonstrated that binding affinity correlated with conformational rigidity, and a hybridization preference for sp2 > S- > R-sp3 semicarbazide nitrogen configuration was evaluated. Evidence of the active conformation and the relevance for dynamic chirality serve as insights for creating cyclic (aza)peptide CD36 modulators to curb inflammation. |
| URL الوصول: |
https://gup.ub.gu.se/publication/291817 |
| قاعدة البيانات: |
SwePub |
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