A new study in Nature Communication has identified several short peptides derived from the chemicals that ticks release to inhibit inflammation at bite sites: the broad-spectrum anti-chemokine activity of these short peptides could be used to develop new treatments for inflammatory diseases such as rheumatoid arthritis.
Inflammatory diseases can be hard to treat, since a key pathway for inflammation is set off by a group of chemicals – chemokines – which have a lot redundancy built in; chemokines play a major role in diseases such as atherosclerosis, rheumatoid arthritis, inflammatory bowel diseases, and cytokine storm. It has been difficult to design treatments to target chemokines because inflammation involves the activation of multiple chemokines with functionally redundant activities, likely because of ‘one to many’ interactions between chemokines and their targets.
However, work from Professor Shoumo Bhattacharya’s lab has previously identified that tick saliva contains components that can bind to these redundant chemokines and successfully inhibit inflammation, allowing ticks to maintain prolonged attachment on animal skin. These ‘evasins’ from tick saliva may therefore hold the key to better treatments for inflammatory diseases.
Evasins themselves have been difficult to use therapeutically, in part because of immune responses that might be triggered by foreign proteins in the body, and their high manufacturing costs. One way to get around these issues is to develop simpler molecules which mimic the inflammation-blocking properties of evasins.
Professor Bhattacharya and his colleagues used a variety of in-vitro techniques to identify short peptides (derived from a class of evasin proteins) that mimic evasins, binding to multiple key chemokines. What’s more, these peptides could bind two different classes of chemokines, unlike the parental chemokine that they were derived from, which could bind to only one.
Further, the group identified the exact arrangement of amino acids that is common to these chemokine-binding short peptides, and used computational modelling to find how these short peptides bind to chemokines to block their activity.
'We think this is a very exciting finding, because scientists now have a template to develop synthetic agents that mimic 3D and physio-chemical properties of evasins,' said Professor Bhattacharya. 'The binding affinity and inhibitory potency of the peptides we have identified is not yet in the range that they could work as treatments, but these could be enhanced with in-vitro molecular evolution that targets these properties.'
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