Scholarlink

Abstract <p><b>Objective:</b> The tetrapeptide Ac–Trp–Pro–Arg–Gly–NH<sub>2</sub>, a <i>C</i>-terminal fragment of arginine vasopressin (AVP), is of high interest as a potential pharmaceutical agent for developing new antidepressant and anxiolytic drugs. In this work we aimed to improve synthetic approach for obtaining the compound and perform its toxicological evaluation. <b>Methods:</b> Ac–Trp–Pro–Arg–Gly–NH<sub>2</sub> was synthesized by classical methods of peptide chemistry using a convergent approach to chain assembly and activated ester and carbodiimide methods as condensation methods. The cytotoxicity of the synthesized peptide against human fibroblast cells was assessed by the MTT assay. Acute toxicity was studied on ICR mice (<i>n</i> = 16 in experimental group; <i>n</i> = 16 in control group) with intranasal administration of the tetrapeptide. The toxicity of Ac–Trp–Pro–Arg–Gly–NH<sub>2</sub> was assessed by monitoring changes in the body weight of rodents and visual changed in their internal organs. <b>Results and Discussion:</b> This study shows that the new “block” scheme allows to produce the tetrapeptide in higher yields (2–3 times) than was shown previously. Ac–Trp–Pro–Arg–Gly–NH<sub>2</sub> demonstrated no cytotoxicity on fibroblasts in the range of expected therapeutic doses (IC<sub>50</sub> &gt;1000 μM) and did not exhibit any clearly expressed pathological effect on the internal organs of experimental mice under conditions of the experiment. <b>Conclusions:</b> The low toxic effects of tryptophan-containing AVP analog demonstrated in this work makes the tetrapeptide a promising substance for further investigations of biological activity, toxicity and mechanisms of action with the aim of creating new, safer and more effective anxiolytics and antidepressants based on the compound.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年12月1日

查看全文
  • K. U. Baradzina,
  • E. I. Kvyatkovskaya,
  • V. P. Martinovich,
  • O. V. Gribovskaya,
  • O. V. Panibrat,
  • T. V. Chukarina,
  • S. E. Ogurtsova,
  • R. D. Zilberman,
  • O. N. Savanets,
  • L. M. Olgometz,
  • A. O. Savin,
  • I. V. Zhebrokova,
  • E. V. Kravchenko

摘要

Abstract

Objective: The tetrapeptide Ac–Trp–Pro–Arg–Gly–NH2, a C-terminal fragment of arginine vasopressin (AVP), is of high interest as a potential pharmaceutical agent for developing new antidepressant and anxiolytic drugs. In this work we aimed to improve synthetic approach for obtaining the compound and perform its toxicological evaluation. Methods: Ac–Trp–Pro–Arg–Gly–NH2 was synthesized by classical methods of peptide chemistry using a convergent approach to chain assembly and activated ester and carbodiimide methods as condensation methods. The cytotoxicity of the synthesized peptide against human fibroblast cells was assessed by the MTT assay. Acute toxicity was studied on ICR mice (n = 16 in experimental group; n = 16 in control group) with intranasal administration of the tetrapeptide. The toxicity of Ac–Trp–Pro–Arg–Gly–NH2 was assessed by monitoring changes in the body weight of rodents and visual changed in their internal organs. Results and Discussion: This study shows that the new “block” scheme allows to produce the tetrapeptide in higher yields (2–3 times) than was shown previously. Ac–Trp–Pro–Arg–Gly–NH2 demonstrated no cytotoxicity on fibroblasts in the range of expected therapeutic doses (IC50 >1000 μM) and did not exhibit any clearly expressed pathological effect on the internal organs of experimental mice under conditions of the experiment. Conclusions: The low toxic effects of tryptophan-containing AVP analog demonstrated in this work makes the tetrapeptide a promising substance for further investigations of biological activity, toxicity and mechanisms of action with the aim of creating new, safer and more effective anxiolytics and antidepressants based on the compound.