Probing the Conformation of a Potent Altered Peptide Ligand, [ARG91, ALA96] MBP87-99: A 2D Spectroscopic and Modelling Study [Abstract]

Mantzourani, Efthymia D. ORCID: https://orcid.org/0000-0002-6313-1409, Tselios, T., Matsoukas, J. and Mavromoustakos, T. 2004. Probing the Conformation of a Potent Altered Peptide Ligand, [ARG91, ALA96] MBP87-99: A 2D Spectroscopic and Modelling Study [Abstract]. Journal of Peptide Science 10 (S2) , p. 275. 10.1002/psc.618

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Abstract

Multiple Sclerosis (MS) is a myelin-specific CD4+ T-cell mediated autoimmune disease that is triggered by unknown exogenous agents, in individuals with a specific genetic background. A novel approach towards the therapeutic management of MS has been launched by the introduction of antigen-specific therapies that suppress autoreactive T cells or switch the immune response from Th1 to Th2. Myelin Basic Protein (MBP) has been considered as a candidate autoantigen, supported by evidence depicting that the epitope MBP72-85 has the potential of inducing Experimental Autoimmune Encephalomyelitis (EAE) when injected in Lewis rats. Within the grounds of actively inhibit the disease, the design and use of peptide analogues of MBP is suggested, exploiting the idea of blocking the formation of the trimolecular complex MHC–APL–TCR. Inference to a series of EAE experiments induced by the MBP72-85 epitope is that a linear Altered Peptide Ligand (APL), [Arg91, Ala96] MBP87-99, holds antagonistic activity. We sought to perform conformational analysis of the APL in order to comprehend the stereoelectronic requirements for antagonism. A combination of 2D NMR spectroscopy and molecular modelling was applied to achieve this aim. ROE data suggest a semicircular conformation, with the backbone of the APL folded and an almost head-to-tail arrangement. Energy minimized structures generated after a molecular modelling theoretical study, supplied conformations akin to the ones generated using distance constraints dictated by 2D ROESY spectroscopy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Additional Information:	Supplement: 3rd International and 28th European Peptide Symposium, September 5–10, 2004; Prague, Czech Republic
Publisher:	Wiley-Blackwell
ISSN:	1099-1387
Last Modified:	19 Oct 2022 08:36
URI:	https://orca.cardiff.ac.uk/id/eprint/18349

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