Selective Inhibitors of T Cell Receptor Recognition of Antigen–MHC Complexes for Rheumatoid Arthritis

Francesco Ria, Gabriele Di Sante, Elisa Gremese, Davide Pirolli, Benedetta Righino, Jacopo Gervasoni, Chiara Nicolo', Bruno Giardina, Gianfranco Ferraccioli, Maria Cristina De Rosa

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Autoreactive T cells specific to human collagen type II have a crucial role in the development of rheumatoid arthritis (RA) in the context of MHC class II allele HLA-DRB1-*04. The protein−protein interactions between the T cell receptor (TCR) and the type II collagen bound to the allele MHC of class II may thus represent the target for the development of new drugs against RA. In this study, a structure-based pharmacophore model for potential small molecule inhibitors was developed from protein−protein interface structure. The 3D model obtained was used for a virtual screening workflow, which resulted in three hits for experimental follow up. Three compounds have been identified that interfere with the TCR/collagenIIMHCII (Ki values below 10 μM) and open up new possibilities in the treatment of RA.
Lingua originaleEnglish
pagine (da-a)644-649
Numero di pagine6
RivistaACS Medicinal Chemistry Letters
Volume10
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • TCR, modeling, rheumatoid arthritis

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