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Synthesis of lipopeptides of the immunodominant epitope hMBP(83–99) containing amide or C-C bond linked hydrophobic chains for the study of T cell response

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Summary

We previously demonstrated that the lipopeptide of the myelin basic protein (MBP) immunodominant epitope in Lewis rat Palm-GpMBP(74-85) (Gp: guinea pig), which induced experimental autoimmune encephalomyelitisin vivo strongly increased the T cell proliferative responsein vitro. We extended this study to the human immunodominant epitope hMBP(83-99), synthesizing different lipophilic peptides bearing a hydrophobic chain linked through an amide or a C-C bond. To this aim, we developed a synthetic pathway for (±)-N-Fmoc-Ahd-OH (Ahd: 2-aminohexadecanoic acid) which was used to synthesize diastereomeric peptides which were successfully separated by reverse-phase high-performance liquid chromatography. MBP-specific T cell lines recognizing the immunodominant epitope hMBP(83-99) have been generated from patients affected by multiple sclerosis. Their proliferative response to the native peptide and to some lipoderivatives has been investigated. In contrast to the animal model, none of the investigated lipopeptides exhibited ‘superagonist’ activity.

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Abbreviations

Ahd:

2-aminohexadecanoic acid

Boc:

tert-butyloxycarbonyl

CNS:

central nervous system

CPM:

count per minute

DCC:

dicyclohexylcarbodiimide

DCM:

dichloromethane

DMAP:

dimethylaminopyridine

DMF:

N,N-dimethylformamide

EAE:

experimental autoimmune encephalomyelitis

ESI-MS:

electrospray ionization mass spectrometry

FAB-MS:

fast-atom-bombardment mass spectrometry

FCC:

flash column chromatography

Fmoc:

fluorenylmethoxycarbonyl

Fmoc-OSu:

N-(9-fluorenylmethoxycarbonyloxy)succinimide

GpMBP:

guinea pig MBP

HATU:

O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate

hMBP:

human MBP

HPLC:

high-performance liquid chromatography

MBP:

myelin basic protein

MHC:

major histocompatibility complex

NMM:

N-methylmorpholine

Palm:

palmitoyl

PBL:

peripheral blood lymphocytes

Pfp:

pentafluorophenyl ester

RP:

reverse phase

SPPS:

solid-phase peptide synthesis

TCL:

T cell line

TCR:

T cell receptor

TFA:

trifluoroacetic acid

TLC:

thin layer chromatography

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Authors and Affiliations

  1. Dipartimento di Chimica Organica ‘Ugo Schiff’ and Centro di Studio sulla Chimica e la Struttura dei Composti Eterociclici e loro Applicazioni, Università di Firenze, Via Gino Capponi 9, I-50121, Florence, Italy

    Silvia Mazzucco, Elena Nardi, Mario Chelli, Mauro Ginanneschi, Gianfranco Rapi & Anna M. Papini

  2. Dipartimento di Scienze Neurologiche e Psichiatriche, Università di Firenze, Viale Pieraccini 6, I-50131, Florence, Italy

    Marco Vergelli, Benedetta Mazzanti, Luca Massacesi & Luigi Amaducci

Authors
  1. Silvia Mazzucco
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  2. Elena Nardi
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  3. Mario Chelli
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  4. Mauro Ginanneschi
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  5. Gianfranco Rapi
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  6. Anna M. Papini
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  7. Marco Vergelli
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  8. Benedetta Mazzanti
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  9. Luca Massacesi
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  10. Luigi Amaducci
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Additional information

Prof. L. Amaducci passed away on 11 January 1998. His memory will hearten those pursuing this research.

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Mazzucco, S., Nardi, E., Chelli, M. et al. Synthesis of lipopeptides of the immunodominant epitope hMBP(83–99) containing amide or C-C bond linked hydrophobic chains for the study of T cell response. Lett Pept Sci 6, 51–59 (1999). https://doi.org/10.1007/BF02443618

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  • DOI: https://doi.org/10.1007/BF02443618

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