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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Tselios, T. | en |
| dc.contributor.author | Probert, L. | en |
| dc.contributor.author | Daliani, I. | en |
| dc.contributor.author | Matsoukas, E. | en |
| dc.contributor.author | Troganis, A. | en |
| dc.contributor.author | Gerothanassis, I. P. | en |
| dc.contributor.author | Mavromoustakos, T. | en |
| dc.contributor.author | Moore, G. J. | en |
| dc.contributor.author | Matsoukas, J. M. | en |
| dc.date.accessioned | 2015-11-24T16:55:22Z | - |
| dc.date.available | 2015-11-24T16:55:22Z | - |
| dc.identifier.issn | 0022-2623 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/10298 | - |
| dc.rights | Default Licence | - |
| dc.subject | multiple-sclerosis patients | en |
| dc.subject | t-cell clones | en |
| dc.subject | angiotensin-ii | en |
| dc.subject | peptide analogs | en |
| dc.subject | rotating frame | en |
| dc.subject | lymphocyte-t | en |
| dc.subject | receptor | en |
| dc.subject | recognition | en |
| dc.subject | spectroscopy | en |
| dc.subject | h-1-nmr | en |
| dc.title | Design and synthesis of a potent cyclic analogue of the myelin basic protein epitope MBP72-85: Importance of the Ala(81) carboxyl group and of at cyclic conformation for induction of experimental allergic encephalomyelitis | en |
| heal.type | journalArticle | - |
| heal.type.en | Journal article | en |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.identifier.primary | Doi 10.1021/Jm980250e | - |
| heal.identifier.secondary | <Go to ISI>://000079636000006 | - |
| heal.identifier.secondary | http://pubs.acs.org/doi/pdfplus/10.1021/jm980250e | - |
| heal.language | en | - |
| heal.access | campus | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας | el |
| heal.publicationDate | 1999 | - |
| heal.abstract | Experimental allergic encephalomyelitis (EAE) is induced in susceptible animals by immunodominant determinants of myelin basic protein (MBP), such as guinea pig sequence MBP72-85. Two linear and one cyclic analogues based on MBP72-85 have been synthesized and evaluated for EAE induction in Lewis rats. The line ar peptide Gln(1)-Lys-(2)Ser(3)-Gln(4)-Arg(5)-Ser(6)-Gln(7)-Asp(8)-Glu(9)-Asn(10)-Pro(11)-Val(12) (1) was found to induce EAE, while substitution of the Asp residue at position 8 with Ala resulted in an analogue (2) which suppressed the induction of EAE by its parent peptide. Nuclear magnetic resonance studies of analogue 1 in dimethyl sulfoxide (DMSO) using TOCSY/ROESY techniques revealed a head-to-tail intramolecular interaction (ROE connectivity between beta Val(12)-gamma Gln(1)), indicating a pseudocyclic conformation for the immunogenic peptide 1. A conformational model was developed using NMR constraints and molecular dynamics. Based on this model, a novel amide-linked cyclic analogue has been designed and synthesized by connecting the side-chain amino and carboxyl groups of Lys and Glu at positions 2 and 9, respectively, of linear analogue 1. The cyclic analogue Gln-Lys-Ser-GLn-Arg-Ser-Gln-Asp-Glu-Asn-Pro-Val-NH2 (3) had similar activity to the linear peptide 1, and the EAE effects induced by cyclic analogue 3 Were completely suppressed by co;injection with the Ala(81)-substituted analogue 2 in Lewis rats. The similar potencies of analogues 1 and 3 support the proposed cyclic comformation suggested for analogue-1 from NMR studies and computer modeling and provides the basis for designing more potent molecules with improved properties such as increased resistance:,to degradation.(15) The present findings suggest that a cyclic conformation for the MBP72-85 epitope positions the carboxyl group of Asp(81) correctly and presumably other side groups of the peptide such as Arg(78) in a manner which enables functional binding of the trimolecular complex MHC-peptide-T cell receptor resulting in EAE. | en |
| heal.publisher | American Chemical Society | en |
| heal.journalName | J Med Chem | en |
| heal.journalType | peer reviewed | - |
| heal.fullTextAvailability | TRUE | - |
| Appears in Collections: | Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά). ΧΗΜ | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Tselios-1999-Design and synthesis.pdf | 359.32 kB | Adobe PDF | View/Open Request a copy |
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