Thermodynamic and kinetic study of the fibrillization of a family of tetrapeptides and its application to self-sorting: what takes so long?

Tena-Solsona, M., Escuder, B., Miravet, J. F., Castelletto, V., Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926 and Dehsorkhi, A. (2015) Thermodynamic and kinetic study of the fibrillization of a family of tetrapeptides and its application to self-sorting: what takes so long? Chemistry of Materials, 27 (9). pp. 3358-3365. ISSN 1520-5002 doi: 10.1021/acs.chemmater.5b00580

Abstract/Summary

Insight is provided into the thermodynamics and kinetics of peptide fibrillization, a process of particular interest in biomedicine due to its direct relationship to amyloid diseases. The studied isomeric tetrapeptides are terminally end-capped and present two hydrophobic phenylalanine residues and two ionizable hydrophilic aspartic acid residues. These compounds form gels in water which are composed of self-assembled fibrillar networks. Potentiometric titrations have afforded acid–base and solubility constants associated with the fibrillization process. A remarkable pKa shift of the peptide side chains is observed linked to aggregation, allowing for fiber formation at pH values around neutrality. The magnitude of the pKa shift is directly related to the solubility of the tetrapeptides, namely, to the free energy change associated with fibrillization. Therefore, potentiometric titration emerges as a simple tool to evaluate the thermodynamic parameters of the process. Additionally kinetic measurements with NMR, fluorescence spectroscopy, and SANS reveal that initial peptide dimerization is most likely to be the fibrillization rate-determining step. The aggregation process in all cases presents a relatively long lag time of ca. 1–3 h and takes more than 8 h to complete. No correlation is observed between kinetic and thermodynamic parameters. Finally, kinetically controlled self-sorting of a mixture of two isomeric tetrapeptides is described.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/73716
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Uncontrolled Keywords	Materials Chemistry, General Chemistry, General Chemical Engineering
Publisher	American Chemical Society
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