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.

Ria, F., Pirolli, D., Di Sante, G., Righino, B., Gremese, E., Gervasoni, J., Nicolò, C., Giardina, B., Ferraccioli, G., De Rosa, M. C., Selective Inhibitors of T Cell Receptor Recognition of Antigen–MHC Complexes for Rheumatoid Arthritis, <<ACS MEDICINAL CHEMISTRY LETTERS>>, 2019; 10 (4): 644-649. [doi:10.1021/acsmedchemlett.8b00601] [http://hdl.handle.net/10807/131197]

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

Ria, Francesco
Primo
;
Pirolli, Davide;Di Sante, Gabriele;Righino, Benedetta;Gremese, Elisa;Gervasoni, Jacopo;Nicolò, Chiara;Giardina, Bruno;Ferraccioli, Gianfranco;De Rosa, Maria Cristina
Ultimo
2019

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.
Inglese
http://pubs.acs.org/journal/amclct
Ria, F., Pirolli, D., Di Sante, G., Righino, B., Gremese, E., Gervasoni, J., Nicolò, C., Giardina, B., Ferraccioli, G., De Rosa, M. C., Selective Inhibitors of T Cell Receptor Recognition of Antigen–MHC Complexes for Rheumatoid Arthritis, <>, 2019; 10 (4): 644-649. [doi:10.1021/acsmedchemlett.8b00601] [http://hdl.handle.net/10807/131197]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/131197
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