Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2

Terentieva, Ekatherine I.; Komleva, Polina D.; Antonova, Sophia M.; Moskaliuk, Vitalii S.; Khotskin, Nikita V.; Shamshurin, Maxim V.; Sokolov, Maxim N.; Kulikov, Alexander V.

doi:10.3390/ijms27083411

Open AccessArticle

Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2

by

Ekatherine I. Terentieva

¹,

Polina D. Komleva

¹

,

Sophia M. Antonova

¹,

Vitalii S. Moskaliuk

¹,

Nikita V. Khotskin

¹,

Maxim V. Shamshurin

²,

Maxim N. Sokolov

²

and

Alexander V. Kulikov

^1,*

¹

The Federal Research Center Institute Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia

²

Nikolaev Institute of Inorganic Chemistry, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(8), 3411; https://doi.org/10.3390/ijms27083411

Submission received: 2 March 2026 / Revised: 27 March 2026 / Accepted: 8 April 2026 / Published: 10 April 2026

(This article belongs to the Special Issue Heterocyclic Compounds: Synthesis, Design, and Biological Activity)

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Abstract

Pharmacological chaperones (PCs)—small molecules that normalize the 3D structure of mutant protein molecules—are promising substances for pharmacological treatment of grave hereditary pathologies. In this study, possible chaperone-like effects of the Fe(II) with tris(1-pyrasolyl)methane complex, [Fe(TPM)₂]Cl₂, on the mutant 447R form of mouse tryptophan hydroxylase 2 (TPH2) in vitro and in vivo were investigated. The experiments were carried out on Balb/c mice homozygous for the mutant TPH2. This complex in concentrations of 0.01, 0.05 and 0.1 mM markedly increased the temperature (T₅₀) and free energy (ΔG) of the mutant TPH2 thermal denaturation in vitro. Seven intramuscular administrations of 30 and 60 mg/kg of [Fe(TPM)₂]Cl₂ markedly increased the TPH2 activity in the midbrain of Balb/c mice. This increase in the TPH2 activity was not accompanied with an increase in the Tph2 gene mRNA and TPH2 protein levels. It is the first demonstration of chaperone-like activity of [Fe(TPM)₂]Cl₂. This complex is a promising chemical for correction of genetic alterations in TPH2 and the associated hereditary psychic disorders.

Keywords: Fe(II) tris(1-pyrazolyl)methane complex; tryptophan hydroxylase 2; thermal stability; activity; brain; mice

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MDPI and ACS Style

Terentieva, E.I.; Komleva, P.D.; Antonova, S.M.; Moskaliuk, V.S.; Khotskin, N.V.; Shamshurin, M.V.; Sokolov, M.N.; Kulikov, A.V. Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2. Int. J. Mol. Sci. 2026, 27, 3411. https://doi.org/10.3390/ijms27083411

AMA Style

Terentieva EI, Komleva PD, Antonova SM, Moskaliuk VS, Khotskin NV, Shamshurin MV, Sokolov MN, Kulikov AV. Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2. International Journal of Molecular Sciences. 2026; 27(8):3411. https://doi.org/10.3390/ijms27083411

Chicago/Turabian Style

Terentieva, Ekatherine I., Polina D. Komleva, Sophia M. Antonova, Vitalii S. Moskaliuk, Nikita V. Khotskin, Maxim V. Shamshurin, Maxim N. Sokolov, and Alexander V. Kulikov. 2026. "Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2" International Journal of Molecular Sciences 27, no. 8: 3411. https://doi.org/10.3390/ijms27083411

APA Style

Terentieva, E. I., Komleva, P. D., Antonova, S. M., Moskaliuk, V. S., Khotskin, N. V., Shamshurin, M. V., Sokolov, M. N., & Kulikov, A. V. (2026). Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2. International Journal of Molecular Sciences, 27(8), 3411. https://doi.org/10.3390/ijms27083411

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Fe(II) with Tris(1-pyrazolyl)methane Complex Increases Thermal Stability In Vitro and Activity In Vivo of the Mutant 447R Form of Mouse Tryptophan Hydroxylase 2

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