SELECTION OF AN AMINO ACID SITE WITH ONE OF THE FASTEST CLEAVAGE KINETICS BY THE ENDOSOMAL PROTEASE CATHEPSIN B FOR POTENTIAL USE IN DRUG DELIVERY SYSTEMS
- Authors: Khramtsov Y.V.1, Georgiev G.P.1, Sobolev A.S.1,2
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Affiliations:
- Institute of Gene Biology, RAS
- Lomonosov Moscow State University
- Issue: Vol 509, No 1 (2023)
- Pages: 211-214
- Section: Articles
- URL: https://journals.rcsi.science/2686-7389/article/view/135675
- DOI: https://doi.org/10.31857/S2686738923700166
- EDN: https://elibrary.ru/NBOJNC
- ID: 135675
Cite item
Abstract
Based on known literature data, six peptide sequences were selected that are potentially capable of being rapidly cleaved by the endosomal protease cathepsin B. For comparison, cathepsin B cleavage of common linker sequences, polyglycine and polyglycine-serine, was also studied. Different ends of these peptides were labeled with sulfoCyanine3 and sulfoCyanine5 fluorescent dyes, between which Förster resonant energy transfer (FRET) is possible. The kinetics of cleavage of peptides by cathepsin B was studied on a multimodal plate reader by FRET signal reduction. FKFL and FRRG cleavage sites have been shown to be the most suitable for potential use in various drug delivery systems. These sites are much more efficiently cleaved under slightly acidic conditions of endosomes than at neutral extracellular pH.
Keywords
About the authors
Y. V. Khramtsov
Institute of Gene Biology, RAS
Author for correspondence.
Email: ykhram2000@mail.ru
Russian, Moscow
G. P. Georgiev
Institute of Gene Biology, RAS
Email: alsobolev@yandex.ru
Russian, Moscow
A. S. Sobolev
Institute of Gene Biology, RAS; Lomonosov Moscow State University
Author for correspondence.
Email: alsobolev@yandex.ru
Russian, Moscow; Russian, Moscow
References
- Liu G., Yang L., Chen G., et al. // Front Pharmacol. 2021. V. 12. 735446.
- Sobolev A.S. // Front Pharmacol. 2018. V. 9. 952.
- Kern H.B., Srinivasan S., Convertine A.J., et al. // Mol Pharmaceutics. 2017. V. 14. № 5. P. 1450–1459.
- Bottcher-Friebertshauser E., Garten W., Klenk H.D. // Activation of viruses by host proteases. 2018. Springer. 337 p.
- Jin X., Zhang J., Jin X., et al. // ACS Med Chem Lett. 2020. V. 11. № 8. P. 1514–1520.
- Shim M.K., Park J., Yoon H.Y., et al. // J Contr Rel. 2019. V. 294. P. 376–389.
- Poreba M., Rut W., Vizovisek M., Groborz K., et al. // Chem Sci. 2018. V. 9. P. 2113–2129.
- Jordans S., Jenko-Kokalj S., Kuhl N.M., et al. // BMC Biochemistry. 2009. V. 10, 23.
- Biniossek M.L., Nagler D.K., Becker-Pauly C., et al. // J. Proteome Res. 2011. V. 10. P. 5363.
- Khramtsov Y.V., Vlasova A.D., Vlasov A.V., et al. // Acta Cryst. 2020. V. D76. P. 1270–1279.
- Aggarwal N., Sloane B.F. // Proteomics Clin Appl. 2014. V. 8. P. 427–437.
- Zhang X., Lin Y., Gillies R.J. // J Nucl Med. 2010. V. 51. P. 1167–1170.
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