Cytotoxic cationic peptides as а ligands for receptor nucleolin

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Abstract

Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins.

About the authors

A. A. Lushnikova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: LAN21@yandex.ru
ORCID iD: 0000-0002-7838-1005
Russian Federation

A. V. Kostarev

M.V. Lomonosov Moscow State University

Email: fake@neicon.ru
ORCID iD: 0000-0001-8040-5929
Russian Federation

D. A. Ponkratova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-1624-7556
Russian Federation

A. V. Onyan

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0003-0217-2685
Russian Federation

E. G. Glubokova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-1206-287X
Russian Federation

S. M. Andreev

Immunology Institute, Federal Medical and Biological Agency of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0001-8297-579X
Russian Federation

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