Features of Synthesis and Study of Toxic Properties of Tryptophan-Containing Analogue of Arginine-Vasopressin

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Abstract

Among the previously studied analogues of the C-terminal fragment of arginine vasopressin (AVP), the tetrapeptide Ac-Trp-Pro-Arg-Gly-NH2 is of great interest as a potential pharmaceutical substance. It demonstrated antidepressant-like and anxiolytic activity at doses of 0.10–10 μg/kg in experiments with rodents. In this paper, we consider the features of the synthesis of a tryptophan-containing analogue of AVP, and propose a new "block" scheme for obtaining the peptide, which allows it to be produced in higher yields than shown previously. Experiments were conducted to study the toxic properties of Ac-Trp-Pro-Arg-Gly-NH2. Under these conditions, the peptide did not exhibit any clearly expressed pathological effect on the internal organs of experimental mice, and also showed no cytotoxicity in the range of expected therapeutic doses (IC50 >1000 μM). The low toxic effects of tryptophan-containing AVP analogue demonstrated in this work makes the tetrapeptide a promising substance for further studies of biological activity, toxicity and mechanisms of action with the aim of creating new, safer and more effective anxiolytics and antidepressants based on it.

About the authors

K. V Borodina

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Email: borodina@iboch.by
Minsk, Belarus

E. I Kvyatkovskaya

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

V. P Martinovich

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

O. V Gribovskaya

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

O. V Panibrat

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

T. V Chukarina

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

S. E Ogurtsova

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

R. D Zilberman

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

O. N Savanets

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

L. M Olgometz

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

A. O Savin

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

I. V Zhebrokova

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

E. V Kravchenko

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

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