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Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides

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Abstract

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

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Fig. 1.
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Abbreviations

CP:

cationic peptide

GA:

gallic acid

PBS:

phosphate buffered saline

ROS:

reactive oxygen species

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Funding

This work was supported by the Federal Medical-Biological Agency of Russian Federation ("Dendrimer 21" program).

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Authors and Affiliations

  1. “NRC Institute of Immunology” FMBA of Russia, 115522, Moscow, Russia

    Artem A. Shatilov, Sergey M. Andreev, Anastasiya V. Shatilova, Evgeny A. Turetskiy, Renata A. Kurmasheva, Marina O. Babikhina, Larisa V. Saprygina, Nadezhda N. Shershakova, Dar’ya K. Bolyakina, Valeriy V. Smirnov, Igor P. Shilovsky & Musa R. Khaitov

  2. Sechenov First Moscow State Medical University (Sechenov University), 119435, Moscow, Russia

    Evgeny A. Turetskiy, Renata A. Kurmasheva & Valeriy V. Smirnov

  3. MIREA – Russian Technological University, 119454, Moscow, Russia

    Marina O. Babikhina & Larisa V. Saprygina

  4. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    Musa R. Khaitov

Authors
  1. Artem A. Shatilov
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  2. Sergey M. Andreev
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Contributions

S.M.A. and M.R.Kh. designed and managed the study; A.A.Sh., A.V.Sh., E.A.T., R.A.K., D.K.B., M.O.B., and L.V.S. conducted experiments; N.N.Sh., A.A.T., V.V.S., I.P.Sh., and S.M.A. discussed the results.

Corresponding author

Correspondence to Sergey M. Andreev.

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This work does not contain studies involving human and animal subjects. The authors of this article declare no conflict of interest.

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Shatilov, A.A., Andreev, S.M., Shatilova, A.V. et al. Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides. Biochemistry Moscow 89, 173–183 (2024). https://doi.org/10.1134/S0006297924010115

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