Show simple item record

dc.contributor.authorYannakakis, M-P
dc.contributor.authorSimal, C
dc.contributor.authorTzoupis, H
dc.contributor.authorRodi, M
dc.contributor.authorDargahi, N
dc.contributor.authorPrakash, M
dc.contributor.authorMouzaki, A
dc.contributor.authorPlatts, JA
dc.contributor.authorApostolopoulos, V
dc.contributor.authorTselios, TV
dc.date.accessioned2020-12-21T04:09:38Z
dc.date.available2020-12-21T04:09:38Z
dc.date.issued2017-06-08
dc.identifierpii: ijms18061215
dc.identifier.citationYannakakis, M. -P., Simal, C., Tzoupis, H., Rodi, M., Dargahi, N., Prakash, M., Mouzaki, A., Platts, J. A., Apostolopoulos, V. & Tselios, T. V. (2017). Design and Synthesis of Non-Peptide Mimetics Mapping the Immunodominant Myelin Basic Protein (MBP83-96) Epitope to Function as T-Cell Receptor Antagonists.. Int J Mol Sci, 18 (6), pp.1215-1215. https://doi.org/10.3390/ijms18061215.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11343/257507
dc.description.abstractEncephalitogenic T cells are heavily implicated in the pathogenesis of multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system. Their stimulation is triggered by the formation of a trimolecular complex between the human leukocyte antigen (HLA), an immunodominant myelin basic protein (MBP) epitope, and the T cell receptor (TCR). We detail herein our studies directed towards the rational design and synthesis of non-peptide mimetic molecules, based on the immunodominant MBP83-96 epitope that is recognized by the TCR in complex with HLA. We focused our attention on the inhibition of the trimolecular complex formation and consequently the inhibition of proliferation of activated T cells. A structure-based pharmacophore model was generated, in view of the interactions between the TCR and the HLA-MBP83-96 complex. As a result, new candidate molecules were designed based on lead compounds obtained through the ZINC database. Moreover, semi-empirical and density functional theory methods were applied for the prediction of the binding energy between the proposed non-peptide mimetics and the TCR. We synthesized six molecules that were further evaluated in vitro as TCR antagonists. Analogues 15 and 16 were able to inhibit to some extent the stimulation of T cells by the immunodominant MBP83-99 peptide from immunized mice. Inhibition was followed to a lesser degree by analogues 17 and 18 and then by analogue 19. These studies show that lead compounds 15 and 16 may be used for immunotherapy against MS.
dc.languageeng
dc.publisherMDPI AG
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDesign and Synthesis of Non-Peptide Mimetics Mapping the Immunodominant Myelin Basic Protein (MBP83-96) Epitope to Function as T-Cell Receptor Antagonists.
dc.typeJournal Article
dc.identifier.doi10.3390/ijms18061215
melbourne.affiliation.departmentUniversity General
melbourne.source.titleInternational Journal of Molecular Sciences
melbourne.source.volume18
melbourne.source.issue6
melbourne.source.pages1215-1215
dc.rights.licenseCC BY
melbourne.elementsid1272133
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486038
melbourne.contributor.authorApostolopoulos, Vasso
dc.identifier.eissn1422-0067
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record