Insulin amyloid fibril formation reduction by tripeptide stereoisomers
Source abstract
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.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Supramolecular Self-Assembly in Materials · Alzheimer's disease research and treatments · Protein Structure and Dynamics
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Chemical Pharmaceutical Science Department, University of Trieste, 34127 Trieste, Italy
Materials Synthesis Department, Jožef Stefan, Institute, 1000 Ljubljana, Slovenia
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
Elettra Sincrotrone Trieste, Strada Statale 14 - km 163,5 Basovizza, 34149 Trieste, Italy
Physics Department, University of Cagliari, 09042 Monserrato, Cagliari, Italy
Facultad de Ciencias y Tecnologías Químicas, Instituto Regional de Investigación Científica Aplicada (IRICA), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain
Funding
Fondazione Cassa di Risparmio di Pistoia e Pescia · Elettra-Sincrotrone Trieste · Junta de Comunidades de Castilla-La Mancha · Università degli Studi di Trieste · Fondazione di Sardegna
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