A Chemical Chaperone That Prevents Insulin Fibrillation

13 December 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Insulin, a peptide hormone, is susceptible to amyloid formation upon exposure to aberrant physiological conditions, result-ing in a loss of its bioactivity. For mitigating insulin aggregation, we report a molecule called PAD-S, which completely inhibit-ed insulin fibril formation, and preserved insulin in its soluble form. Circular Dichroism spectroscopy showed that PAD-S was able to maintain the native structure of insulin, thus acting as a chemical chaperone. Seeded aggregation kinetics suggest that PAD-S inhibited primary nucleation events during aggregation. This is consistent with molecular docking results which suggest that PAD-S binds strongly to native insulin monomers/dimers. Through a competitive binding experiment with ‘LVEALYL’ peptide, we conclude that PAD-S likely binds to the amyloid prone B11-B17 residues of insulin thereby prevent-ing its aggregation. PAD-S was also effective in disaggregating preformed insulin fibrils to non-toxic species. PAD-S treated insulin was functional as indicated by its ability to phosphorylate Akt. PAD-S was also highly effective in preventing the ag-gregation of insulin biosimilars. The low cellular cytotoxicity of PAD-S, and amelioration of aggregation-induced toxicity by PAD-S treated insulin further highlights its potential as an effective chemical chaperone.


chemical chaperone


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.