Hydroxyl Groups on Annular Ring-B Dictate the Affinities of Flavonol–CCL2 Chemokine Binding Interactions
Nidhi Joshi, Deepak Kumar Tripathi, Nupur Nagar, Krishna Mohan Poluri
Abstract
μM. The NMR- and computational docking-based outcomes have strongly suggested that the flavonols interact with CCL2, comprising the N-terminal and β1- and β3-sheets. It has also been observed that the number of hydroxyl groups on the annular ring-B imposed a significant cumulative effect on the binding affinities of flavonols for CCL2 chemokine. Further, the binding surface of these flavonols to CCL2 orthologs was observed to be extensively overlapped with that of the receptor/GAG-binding surface, thus suggesting attenuation of CCL2-CCR2/GAG interactions in their presence. Considering the pivotal role of CCL2 during monocyte/macrophage trafficking and the immunomodulatory features of these flavonols, their direct interactions highlight the promising role of flavonols as nutraceuticals.