Issue 1, 2021

Site-specific single point mutation by anthranilic acid in hIAPP8–37 enhances anti-amyloidogenic activity

Abstract

Amylin or hIAPP, together with insulin, plays a significant role in glucose metabolism. However, it undergoes β-sheet rich amyloid formation associated with pancreatic β-cell dysfunction leading to type-2 diabetes (T2D). Recent studies suggest that restricting β-sheet formation in it may halt amyloid formation, which may limit the risk for the disease. Several peptide-based inhibitors have been reported to prevent aggregation. However, most of them have limitations, including low binding efficiency, active only at higher doses, poor solubility, and proteolytic degradation. Insertion of non-coded amino acids renders proteolytically stable peptides. We incorporated a structurally rigid β-amino acid, Anthranilic acid (Ant), at different sites within the central hydrophobic region of hIAPP and developed two singly mutated hIAPP8–37 peptidomimetics. These peptidomimetics inhibited the amyloid formation of hIAPP substantially even at low concentration, as evident from in vitro ThT, CD, FT-IR, TEM, and Congo red staining birefringence results. These peptidomimetics also disrupted the preformed aggregates formed by hIAPP into non-toxic species. These β-amino acid-based peptidomimetics can be an attractive scaffold for therapeutic design towards T2D or other protein misfolding diseases.

Graphical abstract: Site-specific single point mutation by anthranilic acid in hIAPP8–37 enhances anti-amyloidogenic activity

Supplementary files

Article information

Article type
Paper
Submitted
03 Oct 2020
Accepted
24 Dec 2020
First published
15 Jan 2021
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2021,2, 266-273

Site-specific single point mutation by anthranilic acid in hIAPP8–37 enhances anti-amyloidogenic activity

S. Kalita, S. Kalita, A. Paul, M. Shah, S. Kumar and B. Mandal, RSC Chem. Biol., 2021, 2, 266 DOI: 10.1039/D0CB00178C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements