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Novel conformational peptide antigen which simulates an immunodominant epitope of the 2nd extracellular loop of β1-adrenoreceptor: Computer simulation, synthesis, spatial structure

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Abstract

By the means of computer simulation, the polypeptide antigen conformational structure that initiates the immunodominant epitope of the 2nd extracellular loop of β1-adrenoreceptor has been built. A linear 25-member peptide corresponding to the calculated sequence was synthesized by means of the solid-phase method using Fmoc-technology, then by means of the closure of disulfide bridges, the original bicyclic polypeptide was obtained corresponding to the proposed structure of the conformational antigen. With the help of high-resolution NMR spectroscopy, the 3D structure of synthetic conformational antigen was investigated. It was shown, that the structure of bicyclic polypeptide is similar to that of the computer model. Bicyclic conformational antigen was suitable for the detection of autoantibodies in the blood serum of patients with rhythm and conductivity violation without evidence of organic disease of the cardiovascular system.

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Abbreviations

Acm:

acetamidomethyl

Boc:

tert-butoxycarbonyl

DCM:

dichloromethane

DIPEA:

N,N-diisopropylethylamine

DTT:

dithiothreitol

DQFCOSY:

double quantum filtered correlation spectroscopy

Fmoc:

9-fluorenylmethoxycarbonyl

HOBt:

1-hydroxybenzotriazole

HSQC:

heteronuclear single quantum correlation

MALDI:

matrix-assisted laser desorption/ionization

NOESY:

nuclear Overhauser effect NMR spectroscopy

TBTU, N,N,N′,N′:

tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate

Pbf:

2,2,4,6,7-pentameth-yldihydrobenzofuran-5-sulfonyl

TIS:

triisopropylsilane

TFA:

trifluoroacetic acid

TOCSY:

total correlation spectroscopy

Trt:

trityl

IHS:

ischemic heart disease

ELISA:

enzyme-linked immunosorbent assay

RMSD:

root-mean-square deviation

NOE:

nuclear Overhauser effect

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Authors and Affiliations

  1. Russian Cardiology Research and Production Complex, Moscow, 121552, Russia

    R. Sh. Bibilashvili, M. V. Sidorova, A. S. Molokoedov, Zh. D. Bespalova, E. E. Efremov, T. V. Sharf, M. M. Rogova, N. A. Mironova, K. A. Zykov & S. P. Golitsyn

  2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    E. V. Bocharov

  3. Kurchatov Institute, Moscow, 123182, Russia

    E. V. Bocharov

Authors
  1. R. Sh. Bibilashvili
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  2. M. V. Sidorova
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  3. A. S. Molokoedov
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  4. Zh. D. Bespalova
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  5. E. V. Bocharov
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  6. E. E. Efremov
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  7. T. V. Sharf
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  8. M. M. Rogova
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  9. N. A. Mironova
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  10. K. A. Zykov
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  11. S. P. Golitsyn
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Corresponding author

Correspondence to M. V. Sidorova.

Additional information

Original Russian Text © R.Sh. Bibilashvili, M.V. Sidorova, A.S. Molokoedov, Zh.D. Bespalova, E.V. Bocharov, E.E. Efremov, T.V. Sharf, M.M. Rogova, N.A. Mironova, K.A. Zykov, S.P. Golitsyn, 2013, published in Bioorganicheskaya Khimiya, 2013, Vol. 39, No. 6, pp. 658–670.

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Bibilashvili, R.S., Sidorova, M.V., Molokoedov, A.S. et al. Novel conformational peptide antigen which simulates an immunodominant epitope of the 2nd extracellular loop of β1-adrenoreceptor: Computer simulation, synthesis, spatial structure. Russ J Bioorg Chem 39, 588–599 (2013). https://doi.org/10.1134/S1068162013060034

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  • DOI: https://doi.org/10.1134/S1068162013060034

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