Antituberculosis Action of the Synthetic Peptide LKEKK
- Authors: Navolotskaya E.V.1, Zinchenko D.V.1, Kolobov A.A.2, Zolotarev Y.A.3, Murashev A.N.1
-
Affiliations:
- Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry
- State Research Center for Institute of Highly Pure Bioprepararions, FMBA of the Russian Federation
- Institute of Molecular Genetics, Russian Academy of Science
- Issue: Vol 51, No 2 (2025)
- Pages: 352-361
- Section: Articles
- URL: https://gynecology.orscience.ru/0132-3423/article/view/682752
- DOI: https://doi.org/10.31857/S0132342325020139
- EDN: https://elibrary.ru/LBMFXT
- ID: 682752
Cite item
Abstract
In this work, the activity of the synthetic peptide LKEKK was investigated in a mouse model of tuberculosis induced by Mycobacterium bivis-bovinus 8 strain. Therapy with peptide at doses of 0.01, 0.1 and 1 μg/kg (5 daily injections) significantly reduced the lung injury index of mice compared to animals in the control groups (no treatment and isoniazid treatment). Using [3H]LKEKK, it was shown that the high sensitivity of peritoneal macrophages and splenocytes of infected mice to the peptide was maintained for at least three weeks (Kd 18.6 and 16.7 nM for macrophage and splenocyte membranes, respectively).A study of cytokine production by splenocytes of infected mice showed that on the 24th day after treatment with the peptide (doses of 1 and 10 µg/kg) the secretion of IL-2 was restored to the level observed in uninfected animals. IFN-γ production by spleen cells of infected mice also significantly increased upon peptide treatment. At the same time, IL-4 production decreased in splenocytes. In addition, the peptide treatment stimulated the phagocytic activity of peritoneal macrophages, which was reduced due to tuberculosis infection. Thus, the synthetic peptide LKEKK increased the effectiveness of anti-tuberculosis therapy, as well as the strength of the immune response. The peptide can be used in complex therapy of tuberculosis.
Keywords
Full Text

About the authors
E. V. Navolotskaya
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry
Author for correspondence.
Email: navolotskaya@bibch.ru
Russian Federation, prosp. Nauki 6, Pushchino, 142290
D. V. Zinchenko
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry
Email: navolotskaya@bibch.ru
Russian Federation, prosp. Nauki 6, Pushchino, 142290
A. A. Kolobov
State Research Center for Institute of Highly Pure Bioprepararions, FMBA of the Russian Federation
Email: navolotskaya@bibch.ru
Russian Federation, ul. Pudozhskaya 7, St. Petersburg 197110
Y. A. Zolotarev
Institute of Molecular Genetics, Russian Academy of Science
Email: navolotskaya@bibch.ru
Russian Federation, pl. akad. Kurchatova 2, Moscow, 123182
A. N. Murashev
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry
Email: navolotskaya@bibch.ru
Russian Federation, prosp. Nauki 6, Pushchino, 142290
References
- Churchyard G., Kim P., Shah N.S., Rustomjee R., Gandhi N., Mathema B., Dowdy D., Kasmar A., Cardenas V. // J. Infect. Dis. 2017. V. 216. P. S629–S635. https://doi.org/10.1093/infdis/jix362
- Furin J., Cox H., Pai M. // Lancet. 2019. V. 393. P. 1642–1656. https://doi.org/10.1016/S0140-6736(19)30308-3
- Natarajan A., Beena P.M., Devnikar A.V., Mali S. // Indian. J. Tuberc. 2020. V. 67. P. 295–311. https://doi.org/10.1016/j.ijtb.2020.02.005
- Jacobo-Delgado Y.M., Rodríguez-Carlos A., Serrano C.J., Rivas-Santiago B. // Front. Immunol. 2023. V. 14. P. 1194923. https://doi.org/10.3389/fimmu.2023.1194923
- Chiaradia L., Lefebvre C., Parra J., Marcoux J., Burlet-Schiltz O., Etienne G., Tropis M., Daffé M. // Sci. Rep. 2017. V. 7. P. 12807. https://doi.org/10.1038/s41598-017-12718-4
- Stokas H., Rhodes H.L., Purdy G.E. // Tuberculosis. 2020. V. 125. P. 102007. https://doi.org/10.1016/j.tube.2020.102007
- Grzegorzewicz A.E., de Sousa-d’Auria C., McNeil M.R., Huc-Claustre E., Jones V., Petit C., Angala S.K., Zemanová J., Wang Q., Belardinelli J.M., Gao Q., Ishizaki Y., Mikušová K., Brennan P.J., Ronning D.R., Chami M., Houssin C., Jackson M. // J. Biol. Chem. 2016. V. 291. P. 18867–18879. https://doi.org/10.1074/jbc.M116.739227
- Singh P., Rameshwaram N.R., Ghosh S., Mukhopadhyay S. // Future Microbiol. 2018. V. 13. P. 689– 710. https://doi.org/10.2217/fmb-2017-0135
- Singh G., Kumar A., Maan P., Kaur J. // Curr. Drug Targets. 2017. V. 18. P. 1904–1918. https://doi.org/10.2174/1389450118666170711150034
- Khadela A., Chavda V.P., Postwala H., Shah Y., Mistry P., Apostolopoulos V. // Vaccines (Basel). 2022. V. 10. P. 1740. https://doi.org/10.3390/vaccines10101740
- Navolotskaya E.V., Sadovnikov V.B., Zinchenko D.V., Vladimirov V.I., Zolotarev Y.A., Lipkin V.M., Murashev A.N. // Russ. J. Bioorg. Chem. 2019. V. 45. P. 122–128. https://doi.org/10.1134/S1068162019020092
- Navolotskaya E.V., Sadovnikov V.B., Zinchenko D.V., Zav’yalov V.P., Murashev A.N. // J. Clin. Exp. Immunol. 2021. V. 6. P. 356–361. https://doi.org/doi.org/10.33140/JCEI.06.05.02
- Navolotskayaa E.V., Zinchenkoa D.V., Murashev A.N. // Russ. J. Bioorg. Chem. 2023. V. 49. P. 35–40. https://doi.org/10.1134/S106816202301020X
- Navolotskaya E.V., Sadovnikov V.B., Zinchenko D.V., Murashev A.N. // J. Clin. Exp. Immunol. 2023. V. 8. P. 590–595. https://doi.org/10.33140/JCEI.08.03.01
- Ellner J.J. // J. Lab. Clin. Med. 1997. V. 130. P. 469– 475. https://doi.org/10.1016/s0022-2143(97)90123-2
- Estrada García I., Hernández Pando R., Ivanyi J. // Front. Immunol. 2021. V. 12. P. 684200. https://doi.org/10.3389/fimmu.2021.684200
- Torres-Juarez F., Trejo-Martínez L.A., Layseca-Espinosa E., Leon-Contreras J.C., Enciso-Moreno J.A., Hernandez-Pando R., Rivas-Santiago B. // Microb. Pathog. 2021. V. 153. P. 104768. https://doi.org/10.1016/j.micpath.2021.104768
- Kaufmann S.H., Ladel C.H., Flesch I.E. // Ciba Found Symp. 1995. V. 195. P. 123–132. https://doi.org/10.1002/9780470514849.ch9
- Mustafa T., Phyu S., Nilsen R., Jonsson R., Bjune G. // Scand. J. Immunol. 2000. V. 51. P. 548–556. https://doi.org/10.1046/j.1365-3083.2000.00721.x
- Vasiliu A., Martinez L., Gupta R.K., Hamada Y., Ness T., Kay A., Bonnet M., Sester M., Kaufmann S.H.E., Lange C., Mandalakas A.M. // Clin. Microbiol. Infect. 2024. V. 30. P. 1123-1130. https://doi.org/10.1016/j.cmi.2023.10.023
- Lange C., Aaby P., Behr M.A., Donald P.R., Kaufmann S.H.E., Netea M.G., Mandalakas A.M. // Lancet Infect. Dis. 2022. V. 22. P. e2–e12. https://doi.org/10.1016/S1473-3099(21)00403-5
- Baliko Z., Szereday L., Szekeres-Bartho J. // FEMS Immunol. 1998. Med. Microbiol. V. 22. P. 199–204. https://doi.org/10.1111/j.1574-695X.1998.tb01207.x
- Dieli F., Singh M., Spallek R., Romano A., Titone L., Sireci G., Friscia G., Di Sano C., Santini D., Salerno A., Ivanyi J. // Scand. J. Immunol. 2000. V. 52. P. 96–102. https://doi.org/10.1046/j.1365-3083.2000.00744.x
- Tamburini B., Badami G.D., Azgomi M.S., Dieli F., La Manna M.P., Caccamo N. // Tuberculosis (Edinb). 2021. V. 130. P. 102–109. https://doi.org/10.1016/j.tube.2021.102109
- Shiratsuchi H., Okuda Y., Tsuyuguchi I. // Infect. Immun. 1987. V. 55. P. 2126–2131. https://doi.org/10.1128/iai.55.9.2126-2131
- McDyer J.F., Hackley M.N., Walsh T.E., Cook J.L., Seder R.A. // J. Immunol. 1997. V. 158. P. 492–500.
- McDyer J.F., Li Z., John S., Yu X., Wu C.Y., Ragheb J.A. // J. Immunol. 2002. V. 169. P. 2736–2746. https://doi.org/10.4049/jimmunol.169.5.2736
- Bermudez L.E., Stevens P., Kolonoski P., Wu M., Young L.S. // J. Immunol. 1989. V. 143. P. 2996–3000.
- Denis M. // Cell. Immunol. 1991. V. 132. P. 150–157. https://doi.org/10.1016/0008-8749(91)90014-3
- Suárez-Méndez R., García-García I., FernándezOlivera N., Valdés-Quintana M., Milanés-Virelles M.T., Carbonell D., Machado-Molina D., ValenzuelaSilva C.M., López-Saura P.A. // BMC Infect. Dis. 2004. V. 4. P. 44. https://doi.org/10.1186/1471-2334-4-44
- Giosue S., Casarini M., Ameglio F., Zangrilli P., Palla M., Altieri A.M., Bisetti A. // Eur. Cytokine Netw. 2000. V. 11. P. 99–104.
- Kobayashi K., Kasama T. // Nihon Hansenbyo Gakkai Zasshi. 2000. V. 69. P. 77–82. https://doi.org/10.5025/hansen.69.77
- Greinert U., Ernst M., Schlaak M., Entzian P. // Eur. Respir. J. 2001. V. 17. P. 1049–1051. https://doi.org/10.1183/09031936.01.17510490
- Phyu S., Tadesse A., Mustafa T., Tadesse S., Jonsson R., Bjune G. // Scand. J. Immunol. 2000. V. 51. P. 147–154. https://doi.org/10.1046/j.1365-3083.2000.00662.x
- Beltan E., Horgen L., Rastogi N. // Microb. Pathog. 2000. V. 28. P. 313–318. https://doi.org/10.1006/mpat.1999.0345
- Ragno S., Romano M., Howell S., Pappin D.J., Jenner P.J., Colston M.J. // Immunol. 2001. V. 104. P. 99–108. https://doi.org/10.1046/j.0019-2805.2001.01274.x
- Zolotarev Y.A., Dadayan A.K., Bocharov E.V., Borisov Y.A., Vaskovsky B.V., Dorokhova E.M., Myasoedov N.F. // Amino Acids. 2003. V. 24. P. 325–333. https://doi.org/10.1007/s00726-002-0404-7
- Sadovnikov V.B., Navolotskaya E.V. // J. Pept. Sci. 2014. V. 20. P. 212–215. https://doi.org/10.1002/psc.2603
- Sadovnikov V.B., Zinchenko D.V., Navolotskaya E.V. // Russ. J. Bioorg. Chem. 2016. V. 42. P. 269–271. https://doi.org/10.1134/S1068162016030122
- Dal Farra C., Zsurger N., Vincent J.-P., Cupo A. // Peptides. 2000. V. 21. P. 577–587. https://doi.org/10.1016/s0196-9781(00)00182-0
- Lowry O.H., Rosebbrough N.J., Farr O.L., Randal R.J. // J. Biol. Chem. 1951. V. 193. P. 265–275.
- Pennock B.E. // Anal. Biochem. 1973. V. 56. P. 306– 309. https://doi.org/10.1016/0003-2697(73)90195-4
- Cheng Y.C., Prusoff W. // Biochem. Pharmacol. 1973. V. 22. P. 3099–3108. https://doi.org/10.1016/0006-2952(73)90196-2
Supplementary files
