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Antioxidant and detoxifying activities of analogues of the delta sleep inducing peptide

Abstract

Sixteen peptides differing in structure from the delta sleep inducing peptide (DSIP) by one to two substitutions of amino acid residues have been synthesized to study the possibility of their application in oncology. The antioxidant properties of the peptides in vitro and their detoxifying activity in vivo have been examined on a model of toxicosis caused by cisplatin, a cytostatic drug widely used in the therapy of tumor diseases. It has been shown that almost all DSIP analogues examined exhibit a direct antioxidant activity, with the activity of the ID-6 analogue being higher than that of DSIP and comparable with that of vitamin C and β-carotene. This analogue shows the most pronounced detoxifying activity toward the action of cisplatin, which manifests itself as a decrease in the death of animals from acute toxicity to 17% compared to 50–67% in the control and the restoration of some biochemical parameters of blood, in particular, a decrease in the activity of the enzymes, aspartate and alanine aminotransferases, and the concentration of the end products of nitrogen exchange: creatinine and urea. Thus, the peptides of the DSIP family may appear promising agents for decreasing the toxic effects of cytostatics used in oncology.

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Abbreviations

AlT:

alanine aminotransferase

AsT:

aspartate aminotransferase

DIEA:

diizopropylethylamine

DSIP:

delta sleep inducing peptide

cHex:

cyclohexyl

Fmoc:

fluorenylme-thyloxycarbonyl

GABA:

γ-aminobutyric acid

HBTU:

2-(1-hydroxybenzotriazolyl)-1,1,3,3-tetramethyluronium hexafluorophosphate

MDA:

malonic dialdehyde

TFA:

trifluoroacetic acid

AOA:

antioxidant activity

LP:

lipid peroxidation

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Correspondence to I. I. Mikhaleva.

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Original Russian Text © I.I. Mikhaleva, V.T. Ivanov, L.V. Onoprienko, I.A. Prudchenko, L.D. Chikin, R.I. Yakubovskaya, E.R. Nemtsova, O.A. Bezborodova, 2014, published in Bioorganicheskaya Khimiya, 2014, Vol. 40, No. 1, pp. 3–11.

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Mikhaleva, I.I., Ivanov, V.T., Onoprienko, L.V. et al. Antioxidant and detoxifying activities of analogues of the delta sleep inducing peptide. Russ J Bioorg Chem 40, 1–8 (2014). https://doi.org/10.1134/S1068162014010087

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  • DOI: https://doi.org/10.1134/S1068162014010087

Keywords

  • delta sleep inducing peptide
  • analogues
  • antioxidant activity
  • detoxifying activity
  • peptides
  • synthesis
  • lipid peroxidation
  • cisplatin