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

作　　者：Rita Cimino Marco Savioli Noemi Ferrante Carrante Ernesto Placidi Hilda Garay-Perez Matilde López-Abad Alexis Musacchio Lasa Maria Del Carmen Domínguez-Horta Emanuela Gatto Francesca Cavalieri Gianfranco Bocchinfuso Mariano Venanzi 

机构地区：[1]PEPSA-LAB,Department of Chemical Sciences and Technology,University of Rome Tor Vergata,Via della Ricerca Scientifica 1,00133,Rome,Italy [2]Department of Physics,University of Rome‘Sapienza’,P.le A.Moro 5,00185 Rome,Italy [3]Centre for Genetic Engineering and Biotechnology,PO Box 6162,10600,Havana,Cuba [4]School of Science,RMIT University,Melbourne,VIC 3001,Australia

出　　处：《ChemPhysMater》2022年第1期62-70,共9页化学物理材料（英文）

基　　金：This project received funding from the European Union Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement no.872233(“PEPSA-MATE”).GB acknowledges CINECA and the EU-PRACE program for the CPU time.FC acknowledges the funding received as an award of an RMIT senior vice chancellor fel-lowship.

摘　　要：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=123μM),ultimately leading to the fibrillization of CIGB-814(cac’=508μM).These results pave the way for a deeper understanding of the CIGB-814 therapeutic activity and may give important insights on its pharmacokinetics.

关 键 词：Molecular dynamics of peptide oligomers Peptide aggregation Peptide fibrils Peptide nanostructures Therapeutic peptides Treatment of rheumatoid arthritis 

分 类 号：O62[理学—有机化学]