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Rybchenko V. S. Panina A. A. Novoseletsky N. V. Balabashin D. S. Yakimov S. A. Solopova O. N. Sveshnikov P. G. Aliev T. K. Dolgikh D. A. Kirpichnikov M. P. 《Russian Journal of Bioorganic Chemistry》2020,46(5):778-786
Russian Journal of Bioorganic Chemistry - Humanization of antibodies for the development of novel therapeutic agents with low immunogenicity remains a topical problem in modern science. In the... 相似文献
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Larina M. V. Finashutina Y. P. Lyzhko N. A. Misyurin V. A. Novoseletsky V. N. Dolgikh D. A. Solopova O. N. Moysenovich A. M. Balabashin D. S. Aliev T. K. Misyurin A. V. Kirpichnikov M. P. 《Russian Journal of Bioorganic Chemistry》2022,48(2):360-371
Russian Journal of Bioorganic Chemistry - The PRAME antigen, which is a significant target for monoclonal antibodies, is a tumor-specific marker that is active at all stages of tumor cell... 相似文献
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A. D. Volyntseva V. N. Novoseletsky K. V. Shaitan A. V. Feofanov 《Moscow University Biological Sciences Bulletin》2017,72(1):25-29
The Kv1.3 voltage-gated potassium channel is involved in a number of processes in excitable and nonexcitable cells: maintenance of resting membrane potential, signal transduction, apoptosis, regulation of cell volume, activation and proliferation of white blood cells. Blocking this channel is an effective approach for the treatment of autoimmune, oncological, chronic inflammatory, and metabolic diseases. The most prospective blockers of Kv1.3 are toxins isolated from the venom of scorpions. Knowledge of the molecular aspects of binding of peptide blockers with the channel is an important condition for the creation of highly effective and selective ligands. In the present work, a complex of hybrid channel KcsA-Kv1.3 with agitoxin 2 was built using homology modeling and molecular dynamics simulation. Analysis of formed contacts allowed us to reveal a complete pattern of interactions and to identify key residues that are responsible for the toxin binding affinity. Results of computational experiment are consistent with the experimental data and important for drug development. 相似文献
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Petrovskaya LE Shingarova LN Kryukova EA Boldyreva EF Yakimov SA Guryanova SV Novoseletsky VN Dolgikh DA Kirpichnikov MP 《Biochemistry. Biokhimii?a》2012,77(1):62-70
Tumor necrosis factor (TNF) plays a key role in the pathogenesis of various diseases. To study the possibility of constructing
TNF-binding proteins by grafting hypervariable regions of immunoglobulins (CDR), we have replaced amino acid sequences of
loops from the tenth type III domain of human fibronectin (10Fn3) by amino acid sequences of CDR from the light and heavy chains of the anti-TNF antibody F10. The assessment of TNF-binding
properties of the resulting proteins by ELISA has revealed the highest activity of Hd3 containing sequences CDR-H1 and CDR-H2
of the antibody F10 and of Hd2 containing sequences CDR-H1 and CDR-H3. The proteins constructed by us on the fibronectin domain
scaffold specifically bound TNF during Western blotting and also weakened its cytotoxic effect on L929 line cells. The highest
neutralizing activity was demonstrated by the proteins Hd2 and Hd3, which induced, respectively, 10- and 50-fold increase
in the EC50 of TNF. 相似文献
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V. N. Novoseletsky A. D. Volyntseva K. V. Shaitan O. S. Sokolova 《Moscow University Biological Sciences Bulletin》2017,72(2):69-73
A voltage-gated potassium channel Kv10.2 is expressed in the nervous system, but its functions and involvement in the development of human disease remain poorly understood. Mutant forms of the Kv10.2 channel were found in patients with epileptic encephalopathy and autism. Molecular modeling of the channel spatial structure is an important tool for gaining knowledge about the molecular aspects of the channel functioning and mechanisms responsible for pathogenesis. In the present work, molecular modeling of the helical fragment of the human Kv10.2 (hEAG2) C-terminal domain in dimeric, trimeric, and tetrameric forms was performed. The stability of all forms was confirmed by molecular dynamics simulation. Contacts and interactions, stabilizing the structure, were identified. 相似文献
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