The biological properties of therapeutic peptides, such as their pharmacokinetics and pharmacodynamics, are correlated with their structure and aggregation properties. Herein, we studied the aggregation properties of a therapeutic peptide (CIGB-814), currently in phase 2 clinical trial, for the treatment of rheumatoid arthritis over a wide range of concentrations (μM–mM). We applied spectroscopic techniques (fluorescence, circular dichro- ism, resonance, and dynamic light scattering), atomic force microscopy, and molecular dynamics simulations to determine the aggregation mechanism of CIGB-814. We found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide oligomers. Subsequently, the peptide oligomers trigger the nucleation and growth of peptide nanostructures (cac = 123 μM), ultimately leading to the fibrillization of CIGB-814 (cac’ = 508 μM). These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.

Cimino, R., Savioli, M., Carrante, N.f., Placidi, E., Garay-Perez, H., López-Abad, M., et al. (2022). Aggregation properties of a therapeutic peptide for rheumatoid arthritis: a spectroscopic and molecular dynamics study. CHEMPHYSMATER, 1, 62-70 [10.1016/j.chphma.2021.09.007].

Aggregation properties of a therapeutic peptide for rheumatoid arthritis: a spectroscopic and molecular dynamics study

Gatto, Emanuela
Membro del Collaboration Group
;
Cavalieri, Francesca
Membro del Collaboration Group
;
Bocchinfuso, Gianfranco
Membro del Collaboration Group
;
Venanzi, Mariano
Writing – Original Draft Preparation
2022-01-01

Abstract

The biological properties of therapeutic peptides, such as their pharmacokinetics and pharmacodynamics, are correlated with their structure and aggregation properties. Herein, we studied the aggregation properties of a therapeutic peptide (CIGB-814), currently in phase 2 clinical trial, for the treatment of rheumatoid arthritis over a wide range of concentrations (μM–mM). We applied spectroscopic techniques (fluorescence, circular dichro- ism, resonance, and dynamic light scattering), atomic force microscopy, and molecular dynamics simulations to determine the aggregation mechanism of CIGB-814. We found that the hierarchical aggregation of CIGB-814 at micromolar concentrations was initiated by the formation of peptide oligomers. Subsequently, the peptide oligomers trigger the nucleation and growth of peptide nanostructures (cac = 123 μM), ultimately leading to the fibrillization of CIGB-814 (cac’ = 508 μM). These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.
2022
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/02 - CHIMICA FISICA
English
Molecular dynamics of peptide oligomers Peptide aggregation; Peptide fibrils; Peptide nanostructures; Therapeutic peptides; Treatment of rheumatoid arthritis
Cimino, R., Savioli, M., Carrante, N.f., Placidi, E., Garay-Perez, H., López-Abad, M., et al. (2022). Aggregation properties of a therapeutic peptide for rheumatoid arthritis: a spectroscopic and molecular dynamics study. CHEMPHYSMATER, 1, 62-70 [10.1016/j.chphma.2021.09.007].
Cimino, R; Savioli, M; Carrante, Nf; Placidi, E; Garay-Perez, H; López-Abad, M; Lasa, Am; Domínguez-Horta, Mdc; Gatto, E; Cavalieri, F; Bocchinfuso, G; Venanzi, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/284477
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