Email this article Synthesis and Biological Properties of a Number of Analogs of DSIP and Its KND Endogenous Prototype
- Authors: Prudchenko I.A.1, Onoprienko L.V.1, Lobanov A.V.2, Rodionov A.N.2, Tukhovskaya E.A.2, Khokhlova O.N.2, Shykhutdinova E.R.2, Murashev A.N.2, Ivanov V.T.1, Mikhaleva I.I.1
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Affiliations:
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
- Issue: Vol 44, No 6 (2018)
- Pages: 631-639
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229042
- DOI: https://doi.org/10.1134/S1068162018060067
- ID: 229042
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Abstract
We performed a computer search for the DSIP homologous structures in the protein data bases and found the KND peptide (WKGGDNASGE), which was closely structurally related to DSIP, corresponding to the 324–332 fragment of the human lysine-specific histone demethylase 3B (EC 1.14.11), and possibly was a prototype of the real endogenous DSIP. Previously, we compared some biological effects of DSIP and KND. Antioxidant, anticonvulsant, and behavioral effects of KND proved to be more pronounced than those of DSIP, suggesting the higher efficacy and therapeutic potential of KND and its derivatives. In this study, we synthesized new analogs of DSIP and KND and examined their detoxifying action after the treatment with the cisplatin cytostatin in comparative experiments in vivo on rodents. KND and several its analogs were found to decrease the cisplatin effects on the induced changes in masses of target organs. The correcting effects of the studied peptides on the cisplatin-induced hematological abnormalities, such as the changes in the leukocyte content in blood and thrombocytopenia, were revealed after their intranasal administration to animals in low doses. A decrease in a pronouncement of histological deviation from a norm was shown in the tissues of liver, kidney, and spleen. A significant hepatoprotective and nephroprotective effects of the studied peptides were also observed. Thus, the revealed antitoxic properties of DSIP, KND, and their analogs, could be a basis for the creation of drugs of lower toxicity in the anticancer treatment and therapy of medicinal hepatitis.
About the authors
I. A. Prudchenko
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: onolv@mail.ru
Russian Federation, Moscow, 117997
L. V. Onoprienko
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Author for correspondence.
Email: onolv@mail.ru
Russian Federation, Moscow, 117997
A. V. Lobanov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
A. N. Rodionov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
E. A. Tukhovskaya
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
O. N. Khokhlova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
E. R. Shykhutdinova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
A. N. Murashev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch)
Email: onolv@mail.ru
Russian Federation, Pushchino, Moscow oblast, 142290
V. T. Ivanov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: onolv@mail.ru
Russian Federation, Moscow, 117997
I. I. Mikhaleva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Email: onolv@mail.ru
Russian Federation, Moscow, 117997
