Issue 23, 2024

Insulin amyloid fibril formation reduction by tripeptide stereoisomers

Abstract

Insulin fibrillation is a problem for diabetic patients that can occur during storage and transport, as well as at the subcutaneous injection site, with loss of bioactivity, inflammation, and various adverse effects. Tripeptides are ideal additives to stabilise insulin formulations, thanks to their low cost of production and inherent cytocompatibility. In this work, we analysed the ability of eight tripeptide stereoisomers to inhibit the fibrillation of human insulin in vitro. The sequences contain proline as β-breaker and Phe–Phe as binding motif for the amyloid-prone aromatic triplet found in insulin. Experimental data based on spectroscopy, fluorescence, microscopy, and calorimetric techniques reveal that one stereoisomer is a more effective inhibitor than the others, and cell live/dead assays confirmed its high cytocompatibility. Importantly, in silico data revealed the key regions of insulin engaged in the interaction with this tripeptide, rationalising the molecular mechanism behind insulin fibril formation reduction.

Graphical abstract: Insulin amyloid fibril formation reduction by tripeptide stereoisomers

Supplementary files

Article information

Article type
Paper
Submitted
18 2 2024
Accepted
05 5 2024
First published
06 5 2024
This article is Open Access
Creative Commons BY license

Nanoscale, 2024,16, 11081-11089

Insulin amyloid fibril formation reduction by tripeptide stereoisomers

B. Rosetti, S. Kralj, E. Scarel, S. Adorinni, B. Rossi, A. V. Vargiu, A. M. Garcia and S. Marchesan, Nanoscale, 2024, 16, 11081 DOI: 10.1039/D4NR00693C

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