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Single mutation in peptide inhibitor of TRPV1 receptor changes its effect from hypothermic to hyperthermic level in animals

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Abstract

The TRPV1 receptor plays a significant role in many biological processes, such as perception of external temperature (above 43°C), inflammation development, and thermoregulation. Activation of TRPV1 leads to the pain occurrence and decrease in the body temperature, while inhibition of this receptor can lead to an increase in the temperature. The TRPV1 peptide modulators from sea anemone Heteractis crispa extract (APHC1 and APHC3) have been previously characterized as molecules, which generated a pronounced analgesic effect and a decrease in the body temperature in experimental animals. Using the combined APHC1 and APHC3 amino acid sequences, we have prepared a hybrid peptide molecule named A13 that contains all residues potentially important for the activity of the peptide precursors. Biological tests on animals have shown that the hybrid molecule not only combines the analgesic properties of both peptides but, unlike the peptide precursors, also raises the body temperature of experimental animals.

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Abbreviations

TRPV1:

vanilloid receptor 1

IPTG:

isopropyl-ß- D-1-thiogalactopyranoside

CFA:

complete Freund’s adjuvant

TFA:

trifluoroacetic acid.

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Authors and Affiliations

  1. Branch of the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    I. A. Dyachenko, V. A. Palikov, Yu. A. Palikova, G. I. Belous & A. N. Murashev

  2. Pushchino State Institute of Natural Science, Pushchino, Moscow oblast, 142290, Russia

    I. A. Dyachenko, V. A. Palikov, Yu. A. Palikova, G. I. Belous & A. N. Murashev

  3. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    Ya. A. Andreev, Yu. A. Logashina, E. E. Maleeva, E. V. Grishin & S. A. Kozlov

  4. Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow, 119991, Russia

    Ya. A. Andreev & Yu. A. Logashina

  5. Russian University of Peoples’ Friendship, Moscow, 117198, Russia

    Ya. A. Andreev

  6. Pushchino Scientific Center of the Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    I. A. Dyachenko & A. N. Murashev

Authors
  1. I. A. Dyachenko
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  2. V. A. Palikov
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  3. Yu. A. Palikova
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  4. G. I. Belous
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  5. A. N. Murashev
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  6. Ya. A. Andreev
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  7. Yu. A. Logashina
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  8. E. E. Maleeva
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  9. E. V. Grishin
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  10. S. A. Kozlov
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Corresponding author

Correspondence to S. A. Kozlov.

Additional information

Original Russian Text © I.A. Dyachenko, V.A. Palikov, Yu.A. Palikova, G.I. Belous, A.N. Murashev, Ya.A. Andreev, Yu.A. Logashina, E.E. Maleeva, E.V. Grishin, S.A. Kozlov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 5, pp. 482–490.

Deceased.

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Dyachenko, I.A., Palikov, V.A., Palikova, Y.A. et al. Single mutation in peptide inhibitor of TRPV1 receptor changes its effect from hypothermic to hyperthermic level in animals. Russ J Bioorg Chem 43, 509–516 (2017). https://doi.org/10.1134/S1068162017050053

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  • DOI: https://doi.org/10.1134/S1068162017050053

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