foodsystFood systemsПищевые системы2618-97712618-7272Федеральный научный центр пищевых систем им. В.М. Горбатова РАН10.21323/2618-9771-2024-7-2-220-224foodsyst-483Research ArticleСтатьиMolecular peptide grafting as a tool for creating new generation of biopeptides: A mini-reviewМолекулярная пептидная трансплантация как инструмент создания биопептидов нового поколения: мини-обзорhttps://orcid.org/0000-0003-4298-0927ЧернухаИ. М.ChernukhaI. M.

Чернуха Ирина Михайловна — доктор технических наук, профессор, академик РАН, главный научный сотрудник, Руководитель Отдела коор-динации инициативных и международных проектов.

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Irina M. Chernukha - Doctor of Technical Sciences, Professor, Academician of the Russian Academy of Sciences, Principal Researcher, Head of the Department for Coordination of Initiative and International Projects, V.M. Gorbatov Federal Research Center for Food Systems.

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i.chernuha@fncps.ruhttps://orcid.org/0000-0003-4863-9834ТихоновС. Л.TikhonovS. L.

Тихонов Сергей Леонидович — доктор технических наук, профессор, директор научно-образовательного центра «Прикладные нанобиотехнологии», Уральский ГАУ; профессор кафедры химической технологии древесины, биотехнологии и наноматериалов, УГЛТУ.

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Sergey L. Tikhonov - Doctor of Technical Sciences, Professor, Director of the Scientific and Educational Center «Applied Nanobiotechnology», Ural State Agricultural University; Professor, Department of Chemical Technology of Wood, Biotechnology and Nanomaterials Ural State Forestry University

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tihonov75@bk.ruhttps://orcid.org/0000-0001-5841-1791ТихоноваН. В.TikhonovaN. V.

Тихонова Наталья Валерьевна — доктор технических наук, заведующий кафедрой пищевой инженерии аграрного производства.

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tihonov75@bk.ruФедеральный научный центр пищевых систем им. В.М. ГорбатоваРоссияV.M. Gorbatov Federal Research Center for Food SystemsRussian FederationУральский государственный аграрный университет; Уральский государственный лесотехнический университетРоссияUral State Agricultural University; Ural State Forestry UniversityRussian FederationУральский государственный аграрный университетРоссияUral State Agricultural UniversityRussian Federation20241607202472220224Copyright © Chernukha I.M., Tikhonov S.L., Tikhonova N.V., 20242024Чернуха И.М., Тихонов С.Л., Тихонова Н.В.Chernukha I.M., Tikhonov S.L., Tikhonova N.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.fsjour.com/jour/article/view/483

Molecular peptide grafting (MPG) is the isolation/synthesis of a bioactive fragment of a peptide/protein and its subsequent transfer to a target protein/peptide to create a new protein product with specified unique biological properties. This is one of the methods together with molecular stapling and peptide backbone circularization to strengthen the structural organization of short peptides. Nowadays research on MPT is mainly focused on demonstrating its usefulness and applicability, rather than on the development of next-generation biopeptides. The purpose of the mini-review is to demonstrate the applicability of MPT to create stable and bioavailable peptides of a new generation with enhanced biological properties. Choosing the right scaffold for subsequent inoculation of a biologically active peptide sequence into it is the most important task in creating targeted biopeptides. Peptides with the necessary framework, such as cyclotides, can be obtained by three-phase synthesis. Cyclotides have a common mechanism of action. Their biological activity is determined both by the ability to bind proteins with the formation of pores and destruction of biological target-membranes, and by the properties necessary to create new peptides in the scaffold. Various peptide inserts can be used to ensure the functionality of new biopeptides obtained by the MPT method. Different peptide drugs are an example of the effective practical use of MTP. Consequently, MPT makes it possible to effectively design a new generation of biopeptides characterized by high epitope thermodynamic and metabolic stability with new or enhanced biological functions. However, the effectiveness of the peptides obtained by the MPT must be proved in vitro and in vivo.

Молекулярная пептидная трансплантация (МПТ) — это выделение/синтез биоактивного фрагмента пептида/белка и последующий перенос его в целевой белок/пептид для создания нового белкового продукта, обладающего заданными уникальными биологическими свойствами. Это один из способов, наряду с методами циркуляризации пептидной основы и молекулярным сшиванием, направленных на усиление структурной организации коротких пептидов. Исследования МПТ в настоящее время в основном сосредоточены на демонстрации ее полезности и применимости, а не на разработке получения биопептидов нового поколения. Цель мини-обзора — показать применимость метода МПТ для разработки стабильных и биодоступных пептидов нового поколения с улучшенными биологическими свойствами. Для создания таких пептидов важно правильно подобрать каркас для последующей прививки к нему биологически активной пептидной последовательности. К пептидам с необходимым каркасом относятся циклотиды, которые можно получить трехфазным синтезом. Циклотиды обладают общим механизмом действия. Их биологическая активность определяется способностью связывать белки с образованием пор и разрушением биологических мембран-мишеней, а также свойствами, необходимыми для создания на их каркасе новых пептидов. Для обеспечения функциональности новых биопептидов, полученных методом МПТ, можно использовать различные пептидные вставки. Примером эффективного практического применения МПТ являются различные пептидные лекарства. Следовательно, МПТ позволяет эффективно конструировать биопептиды нового поколения, отличающиеся высокой термодинамической и метаболической стабильностью эпитопа и новыми или усиленными биологическими функциями. Однако эффективность полученных пептидов с использованием МПТ необходимо доказать в исследованиях in vitro и in vivo.

молекулярная пептидная трансплантациябиопептидыкаркасыпептидные вставкибиологическая активностьmolecular peptide graftingbiopeptidesscaffoldspeptide insertsbiological activityReferencesCamarero, J. A., Campbell, M. J. (2019). The potential of the cyclotide scaffold for drug development. Biomedicines, 7(2), Article 31. https://doi.org/10.3390/biomedicines7020031Camarero, J. A., Campbell, M. J. (2019). The potential of the cyclotide scaffold for drug development. Biomedicines, 7(2), Article 31. https://doi.org/10.3390/biomedicines7020031Wang, C. K., Craik, D. J. (2021). Linking molecular evolution to molecular grafting. Journal of Biological Chemistry, 296, Article 100425. https://doi.org/10.1016/j.jbc.2021.100425Wang, C. K., Craik, D. J. (2021). Linking molecular evolution to molecular grafting. Journal of Biological Chemistry, 296, Article 100425. https://doi.org/10.1016/j.jbc.2021.100425Jacob, B., Vogelaar, A., Cadenas, E., Camarero, J. A. (2022). Using the cyclotide scaffold for targeting biomolecular interactions in drug development. Molecules, 27(19), Article 6430. https://doi.org/10.3390/molecules27196430Jacob, B., Vogelaar, A., Cadenas, E., Camarero, J. A. (2022). Using the cyclotide scaffold for targeting biomolecular interactions in drug development. Molecules, 27(19), Article 6430. https://doi.org/10.3390/molecules27196430Wang, L., Wang, N., Zhang, W., Cheng, X., Yan, Z., Shao, G. et al. (2022). Therapeutic peptides: Current applications and future directions. Signal Transduction and Targeted Therapy, 7, Article 48. https://doi.org/10.1038/s41392-022-00904-4Wang, L., Wang, N., Zhang, W., Cheng, X., Yan, Z., Shao, G. et al. (2022). Therapeutic peptides: Current applications and future directions. Signal Transduction and Targeted Therapy, 7, Article 48. https://doi.org/10.1038/s41392-022-00904-4Sharma, K., Sharma, K. K., Sharma, A., Jain, R. (2023). Peptide-based drug discovery: Current status and recent advances. Drug Discovery Today, 28(2), Article 103464. https://doi.org/10.1016/j.drudis.2022.103464Sharma, K., Sharma, K. K., Sharma, A., Jain, R. (2023). Peptide-based drug discovery: Current status and recent advances. Drug Discovery Today, 28(2), Article 103464. https://doi.org/10.1016/j.drudis.2022.103464Agyei, D., Ahmed, I., Akram, Z., Iqbal, H. M. N., Danquah, M. K. (2017). Protein and peptide biopharmaceuticals: An overview. Protein and Peptide Letters, 24(2), 94-101. https://doi.org/10.2174/0929866523666161222150444Agyei, D., Ahmed, I., Akram, Z., Iqbal, H. M. N., Danquah, M. K. (2017). Protein and peptide biopharmaceuticals: An overview. Protein and Peptide Letters, 24(2), 94-101. https://doi.org/10.2174/0929866523666161222150444Lau, J. L., Dunn, M. K. (2018). Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorganic and Medicinal Chemistry, 26(10), 2700-2707. https://doi.org/10.1016/j.bmc.2017.06.052Lau, J. L., Dunn, M. K. (2018). Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorganic and Medicinal Chemistry, 26(10), 2700-2707. https://doi.org/10.1016/j.bmc.2017.06.052Qin, L., Cui, Z., Wu, Y., Wang, H., Zhang, X., Guan, J. et al. (2022). Challenges and strategies to enhance the systemic absorption of inhaled peptides and proteins. Pharmaceutical Research, 40, 1037-1055. https://doi.org/10.1007/s11095-022-03435-3Qin, L., Cui, Z., Wu, Y., Wang, H., Zhang, X., Guan, J. et al. (2022). Challenges and strategies to enhance the systemic absorption of inhaled peptides and proteins. Pharmaceutical Research, 40, 1037-1055. https://doi.org/10.1007/s11095-022-03435-3Holub, J. M. (2017). Small scaffolds, big potential: Developing miniature proteins as therapeutic agents. Drug Development Research, 78(6), 268-282. https://doi.org/10.1002/ddr.21408Holub, J. M. (2017). Small scaffolds, big potential: Developing miniature proteins as therapeutic agents. Drug Development Research, 78(6), 268-282. https://doi.org/10.1002/ddr.21408Wang, C. K., Craik, D. J. (2021). Linking molecular evolution to molecular grafting. Journal of Biological Chemistry, 296, Article 100425. https://doi.Org/10.1016/j.jbc.2021.100425Wang, C. K., Craik, D. J. (2021). Linking molecular evolution to molecular grafting. Journal of Biological Chemistry, 296, Article 100425. https://doi.Org/10.1016/j.jbc.2021.100425Jacob, B., Vogelaar, A., Cadenas, E., Camarero, J. A. (2022). Using the cyclotide scaffold for targeting biomolecular interactions in drug development. Molecules, 27(19), Article 6430. https://doi.org/10.3390/molecules27196430Jacob, B., Vogelaar, A., Cadenas, E., Camarero, J. A. (2022). Using the cyclotide scaffold for targeting biomolecular interactions in drug development. Molecules, 27(19), Article 6430. https://doi.org/10.3390/molecules27196430Hillman, R. A., Nadraws, J. W., Bertucci, M. A. (2018). The hydrocarbon staple and beyond: Recent advances towards stapled peptide therapeutics that target protein-protein interactions. Current Topics in Medicinal Chemistry, 18(7), 611-624. https://doi.org/10.2174/1568026618666180518095255Hillman, R. A., Nadraws, J. W., Bertucci, M. A. (2018). The hydrocarbon staple and beyond: Recent advances towards stapled peptide therapeutics that target protein-protein interactions. Current Topics in Medicinal Chemistry, 18(7), 611-624. https://doi.org/10.2174/1568026618666180518095255Ali, A. M., Atmaj, J., Van Oosterwijk, N., Groves, M. R., Domling, A. (2019). Stapled peptides inhibitors: A new window for target drug discovery. Computational and Structural Biotechnology Journal, 17, 263-281. https://doi.org/10.1016/j.csbj.2019.01.012Ali, A. M., Atmaj, J., Van Oosterwijk, N., Groves, M. R., Domling, A. (2019). Stapled peptides inhibitors: A new window for target drug discovery. Computational and Structural Biotechnology Journal, 17, 263-281. https://doi.org/10.1016/j.csbj.2019.01.012Chan, A. M., Goodis, C. C., Pommier, E. G., Fletcher, S. (2022). Recent applications of covalent chemistries in protein-protein interaction inhibitors. RSC Medicinal Chemistry, 13(8), 921-928. https://doi.org/10.1039/d2md00112hChan, A. M., Goodis, C. C., Pommier, E. G., Fletcher, S. (2022). Recent applications of covalent chemistries in protein-protein interaction inhibitors. RSC Medicinal Chemistry, 13(8), 921-928. https://doi.org/10.1039/d2md00112hPan, X., Kortemme, T. (2021). Recent advances in de novo protein design: Principles, methods, and applications. Journal of Biological Chemistry, 296, Article 100558. https://doi.org/10.1016/j.jbc.2021.100558Pan, X., Kortemme, T. (2021). Recent advances in de novo protein design: Principles, methods, and applications. Journal of Biological Chemistry, 296, Article 100558. https://doi.org/10.1016/j.jbc.2021.100558Huang, P.-S., Boyken, S. E., Baker, D. (2016). The coming of age of de novo protein design. Nature, 537(7620), 320-327. https://doi.org:10.1038/nature19946Huang, P.-S., Boyken, S. E., Baker, D. (2016). The coming of age of de novo protein design. Nature, 537(7620), 320-327. https://doi.org:10.1038/nature19946Woolfson, D. N. (2021). A brief history of de novo protein design: Minimal, rational, and computational. Journal of Molecular Biology, 433(20), Article 167160. https://doi.org/10.1016/j.jmb.2021.167160Woolfson, D. N. (2021). A brief history of de novo protein design: Minimal, rational, and computational. Journal of Molecular Biology, 433(20), Article 167160. https://doi.org/10.1016/j.jmb.2021.167160Anishchenko, I., Pellock, S.-J., Chidyausiku, T.-M., Ramelot, T.-A., Ovchinnikov, S., Hao, J. et al. (2021). De novo protein design by deep network hallucination. Nature, 600, 547-552. https://doi.org/10.1038/s41586-021-04184-wAnishchenko, I., Pellock, S.-J., Chidyausiku, T.-M., Ramelot, T.-A., Ovchinnikov, S., Hao, J. et al. (2021). De novo protein design by deep network hallucination. Nature, 600, 547-552. https://doi.org/10.1038/s41586-021-04184-wWang, J., Lisanza, S., Juergens, D., Tischer, D., Anishchenko, I., Baek, M. et al. (2022). Scaffolding protein functional sites using deep learning. Science, 377(6604), 387-394. https://doi.org/10.1126/science.abn2100Wang, J., Lisanza, S., Juergens, D., Tischer, D., Anishchenko, I., Baek, M. et al. (2022). Scaffolding protein functional sites using deep learning. Science, 377(6604), 387-394. https://doi.org/10.1126/science.abn2100Marchand, A, Van Hall-Beauvais A. K., Correia, B. E. (2022). Computational design of novel protein-protein interactions — An overview on methodological approaches and applications Current Opinion in Structural Biology, 74, Article 102370. https://doi.org/10.1016/j.sbi.2022.102370Marchand, A, Van Hall-Beauvais A. K., Correia, B. E. (2022). Computational design of novel protein-protein interactions — An overview on methodological approaches and applications Current Opinion in Structural Biology, 74, Article 102370. https://doi.org/10.1016/j.sbi.2022.102370Zhou, W., Smidlehner, T., Jerala, R. (2020). Synthetic biology principles for the design of protein with novel structures and functions. FEBS Letters, 594(14), 2199-2212. https://doi.org/10.1002/1873-3468.13796Zhou, W., Smidlehner, T., Jerala, R. (2020). Synthetic biology principles for the design of protein with novel structures and functions. FEBS Letters, 594(14), 2199-2212. https://doi.org/10.1002/1873-3468.13796Lovelock, S. L., Crawshaw, R., Basler, S., Levy, C., Baker, D., Hilvert D. et al. (2022). The road to fully programmable protein catalysis. Nature, 606, 49-58. https://doi.org/10.1038/s41586-022-04456-zLovelock, S. L., Crawshaw, R., Basler, S., Levy, C., Baker, D., Hilvert D. et al. (2022). The road to fully programmable protein catalysis. Nature, 606, 49-58. https://doi.org/10.1038/s41586-022-04456-zSia, S. K., Carr, P. A., Cochran, A. G., Malashkevich, V. N., Kim, P. S. (2002). Short constrained peptides that inhibit HIV-1 entry. Proceedings of the National Academy of Sciences (PNAS), 99(23), 14664-14669. https://doi.org/10.1073/pnas.232566599Sia, S. K., Carr, P. A., Cochran, A. G., Malashkevich, V. N., Kim, P. S. (2002). Short constrained peptides that inhibit HIV-1 entry. Proceedings of the National Academy of Sciences (PNAS), 99(23), 14664-14669. https://doi.org/10.1073/pnas.232566599Qin, L., Cui, Z., Wu, Y., Wang, H., Zhang, X., Guan, J. et al. (2022). Challenges and strategies to enhance the systemic absorption of inhaled peptides and proteins. Pharmaceutical Research, 40, 1037-1055. https://doi.org/10.1007/s11095-022-03435-3Qin, L., Cui, Z., Wu, Y., Wang, H., Zhang, X., Guan, J. et al. (2022). Challenges and strategies to enhance the systemic absorption of inhaled peptides and proteins. Pharmaceutical Research, 40, 1037-1055. https://doi.org/10.1007/s11095-022-03435-3Wang, C. K., Craik, D. J. (2018). Designing macrocyclic disulfide-rich peptides for biotechnological applications. Nature Chemical Biology, 14, 417-427. https://doi.org/10.1038/s41589-018-0039-yWang, C. K., Craik, D. J. (2018). Designing macrocyclic disulfide-rich peptides for biotechnological applications. Nature Chemical Biology, 14, 417-427. https://doi.org/10.1038/s41589-018-0039-yCrook, Z. R., Sevilla, G. P., Friend, D., Brusniak, M.-Y., Bandaranayake, A. D., Clarke, M. et al. (2017). Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets. Nature Communications, 8, Article 2244. https://doi.org/10.1038/s41467-017-02098-8Crook, Z. R., Sevilla, G. P., Friend, D., Brusniak, M.-Y., Bandaranayake, A. D., Clarke, M. et al. (2017). Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets. Nature Communications, 8, Article 2244. https://doi.org/10.1038/s41467-017-02098-8Simeon, R., Chen, Z. (2018). In vitro-engineered non-antibody protein therapeutics. Protein and Cell, 9(1), 3-14. https://doi.org/10.1007/s13238-017-0386-6Simeon, R., Chen, Z. (2018). In vitro-engineered non-antibody protein therapeutics. Protein and Cell, 9(1), 3-14. https://doi.org/10.1007/s13238-017-0386-6Chiu, M. L., Goulet, D. R., Teplyakov, A., Gilliland, G. L. (2019). Antibody structure and function: The basis for engineering therapeutics. Antibodies, 8(4), Article 55. https://doi.org/10.3390/antib8040055Chiu, M. L., Goulet, D. R., Teplyakov, A., Gilliland, G. L. (2019). Antibody structure and function: The basis for engineering therapeutics. Antibodies, 8(4), Article 55. https://doi.org/10.3390/antib8040055Korendovych, I. V., DeGrado, W. F. (2020). De novo protein design, a retrospective. Quarterly Reviews of Biophysics, 53, Article e3. https://doi.org/10.1017/S0033583519000131Korendovych, I. V., DeGrado, W. F. (2020). De novo protein design, a retrospective. Quarterly Reviews of Biophysics, 53, Article e3. https://doi.org/10.1017/S0033583519000131Bhardwaj, G., Mulligan, V. K., Bahl, C. D., Gilmore, J. M., Harvey, P. J., Cheneval, O.-et al. (2016). Accurate de novo design of hyperstable constrained peptides. Nature, 538, 329-335. https://doi.org/10.1038/nature19791Bhardwaj, G., Mulligan, V. K., Bahl, C. D., Gilmore, J. M., Harvey, P. J., Cheneval, O.-et al. (2016). Accurate de novo design of hyperstable constrained peptides. Nature, 538, 329-335. https://doi.org/10.1038/nature19791Dawson, W. M., Rhys, G. G., Woolfson, D. N. (2019). Towards functional de novo designed proteins. Current Opinion in Chemical Biology, 52, 102-111. https://doi.org/10.1016/j.cbpa.2019.06.011Dawson, W. M., Rhys, G. G., Woolfson, D. N. (2019). Towards functional de novo designed proteins. Current Opinion in Chemical Biology, 52, 102-111. https://doi.org/10.1016/j.cbpa.2019.06.011Garcia, A. E., Camarero, J. A. (2010). Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics. Current Molecular Pharmacology, 3(3), 153-163. https://doi.org/10.2174/1874467211003030153Garcia, A. E., Camarero, J. A. (2010). Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics. Current Molecular Pharmacology, 3(3), 153-163. https://doi.org/10.2174/1874467211003030153Aboye, T., Meeks, C. J., Majumder, S., Shekhtman, A., Rodgers, K., Camarero, J. A. (2016). Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity. Molecules, 21(2), Article 152. https://doi.org/10.3390/molecules21020152Aboye, T., Meeks, C. J., Majumder, S., Shekhtman, A., Rodgers, K., Camarero, J. A. (2016). Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity. Molecules, 21(2), Article 152. https://doi.org/10.3390/molecules21020152Grover, T., Mishra, R., Bushra, Gulati, P., Mohanty, A. (2021). An insight into biological activities of native cyclotides for potential applications in agriculture and pharmaceutics. Peptides, 135, Article 170430. https://doi.org/10.1016/j.peptides.2020.170430Grover, T., Mishra, R., Bushra, Gulati, P., Mohanty, A. (2021). An insight into biological activities of native cyclotides for potential applications in agriculture and pharmaceutics. Peptides, 135, Article 170430. https://doi.org/10.1016/j.peptides.2020.170430Camarero, J. A. (2017). Cyclotides, a versatile ultrastable micro-protein scaffold for biotechnological applications. Bioorganic and Medicinal Chemistry Letters, 27(23), 5089-5099. https://doi.org/10.1016/j.bmcl.2017.10.051Camarero, J. A. (2017). Cyclotides, a versatile ultrastable micro-protein scaffold for biotechnological applications. Bioorganic and Medicinal Chemistry Letters, 27(23), 5089-5099. https://doi.org/10.1016/j.bmcl.2017.10.051Cybase. (2024). The database of cyclic proteins. The Institute of Molecular Biosciences IMG, Brisbane, Australia. Retrieved from https://cybase.org.au Accessed March 04, 2024. Access mode: for registered users.Cybase. (2024). The database of cyclic proteins. The Institute of Molecular Biosciences IMG, Brisbane, Australia. Retrieved from https://cybase.org.au Accessed March 04, 2024. Access mode: for registered users.Li, Y., Bi, T., Camarero, J. A. (2015). Chemical and biological production of cyclotides. Chapter in a book: Advances in Botanical Research. Elsevier Ltd., United Kingdom. 2015. https://doi.org/10.1016/bs.abr.2015.08.006Li, Y., Bi, T., Camarero, J. A. (2015). Chemical and biological production of cyclotides. Chapter in a book: Advances in Botanical Research. Elsevier Ltd., United Kingdom. 2015. https://doi.org/10.1016/bs.abr.2015.08.006Aboye, T., Kuang, Y., Neamati, N., Camarero, J. A. (2015). Rapid parallel synthesis of bioactive folded cyclotides by using a tea-bag approach. ChemBioChem, 16(5), 827-833. https://doi.org/10.1002/cbic.201402691Aboye, T., Kuang, Y., Neamati, N., Camarero, J. A. (2015). Rapid parallel synthesis of bioactive folded cyclotides by using a tea-bag approach. ChemBioChem, 16(5), 827-833. https://doi.org/10.1002/cbic.201402691Li, Y., Gould, A., Aboye, T., Bi, T., Breindel, L., Shekhtman, A. et al. (2017). Full sequence amino acid scanning of theta-defensin RTD-1 yields a potent anthrax lethal factor protease inhibitor. Journal of Medicinal Chemistry, 60(5), 1916-1927. https://doi.org/10.1021/acs.jmedchem.6b01689Li, Y., Gould, A., Aboye, T., Bi, T., Breindel, L., Shekhtman, A. et al. (2017). Full sequence amino acid scanning of theta-defensin RTD-1 yields a potent anthrax lethal factor protease inhibitor. Journal of Medicinal Chemistry, 60(5), 1916-1927. https://doi.org/10.1021/acs.jmedchem.6b01689Montone, C. M., Capriotti, A. L., Cavaliere, C., La Barbera, G., Piovesana S., Chiozzi, R. Z. et al. (2018). Peptidomic strategy for purification and identification of potential ACE-inhibitory and antioxidant peptides in Tetradesmus obliquus microalgae. Analytical and Bioanalytical Chemistry, 410, 3573-3586. http://doi.org/10.1007/s00216-018-0925-xMontone, C. M., Capriotti, A. L., Cavaliere, C., La Barbera, G., Piovesana S., Chiozzi, R. Z. et al. (2018). Peptidomic strategy for purification and identification of potential ACE-inhibitory and antioxidant peptides in Tetradesmus obliquus microalgae. Analytical and Bioanalytical Chemistry, 410, 3573-3586. http://doi.org/10.1007/s00216-018-0925-xLiao, W., Fan, H., Davidge, S. T., Wu, J. (2019). Egg white-derived antihypertensive peptide IRW (Ile-Arg-Trp) reduces blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/Mas receptor axis. Molecular Nutrition and Food Research, 63(9), Article e1900063. https://doi.org/10.1002/mnfr.201900063Liao, W., Fan, H., Davidge, S. T., Wu, J. (2019). Egg white-derived antihypertensive peptide IRW (Ile-Arg-Trp) reduces blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/Mas receptor axis. Molecular Nutrition and Food Research, 63(9), Article e1900063. https://doi.org/10.1002/mnfr.201900063Wisniewski, K., Sueiras-Diaz, J., Jiang, G., Galyean, R., Lu, M., Thompson, D. et al. (2016). Synthesis and pharmacological characterization of novel glucagon-like peptide-2 (GLP-2) analogues with low systemic clearance. Journal of Medicinal Chemistry, 59(7), 3129-3139. https://doi.org/10.1021/acs.jmedchem.5b01909Wisniewski, K., Sueiras-Diaz, J., Jiang, G., Galyean, R., Lu, M., Thompson, D. et al. (2016). Synthesis and pharmacological characterization of novel glucagon-like peptide-2 (GLP-2) analogues with low systemic clearance. Journal of Medicinal Chemistry, 59(7), 3129-3139. https://doi.org/10.1021/acs.jmedchem.5b01909Zhang, Y., Xiu, M, Jiang, J., He, J., Li, D., Liang, S. et al. (2016). Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats. Alcohol, 56, 1-8. https://doi.org/10.1016/j.alcohol.2016.08.003Zhang, Y., Xiu, M, Jiang, J., He, J., Li, D., Liang, S. et al. (2016). Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats. Alcohol, 56, 1-8. https://doi.org/10.1016/j.alcohol.2016.08.003Minshawi F., Lanvermann S., McKenzie E., Jeffery R., Couper K., Papoutsopoulou, S. et al. (2020). The generation of an engineered Interleukin-10 protein with improved stability and biological function. Frontiers in Immunology, 11, Article 1794. https://doi.org/10.3389/fimmu.2020.01794Minshawi F., Lanvermann S., McKenzie E., Jeffery R., Couper K., Papoutsopoulou, S. et al. (2020). The generation of an engineered Interleukin-10 protein with improved stability and biological function. Frontiers in Immunology, 11, Article 1794. https://doi.org/10.3389/fimmu.2020.01794González-Castro, R., Gómez-Lim, M. A., Plisson, F. (2021). Cysteine-rich peptides: Hyperstable scaffolds for protein engineering. ChemBioChem, 22(6), 961-973. https://doi.org/10.1002/cbic.202000634González-Castro, R., Gómez-Lim, M. A., Plisson, F. (2021). Cysteine-rich peptides: Hyperstable scaffolds for protein engineering. ChemBioChem, 22(6), 961-973. https://doi.org/10.1002/cbic.202000634Mehta L, Dhankhar R, Gulati P, Kapoor R. K., Mohanty A., Kumar S. (2020). Natural and grafted cyclotides in cancer therapy: An insight. Journal of Peptide Science, 26(4-5), Article e3246. https://doi.org/10.1002/psc.3246Mehta L, Dhankhar R, Gulati P, Kapoor R. K., Mohanty A., Kumar S. (2020). Natural and grafted cyclotides in cancer therapy: An insight. Journal of Peptide Science, 26(4-5), Article e3246. https://doi.org/10.1002/psc.3246Hamad, F., Elnour, A. A., Elamin, A., Mohamed, S., Yousif, I., Don, J. et al. (2021). Systematic review of glucagon like peptide one receptor agonist liraglutide for subjects with heart failure with reduced left ventricular ejection fraction. Current Diabetes Reviews, 17(3), 280-292. https://doi.org/10.2174/1573399816999200821164129Hamad, F., Elnour, A. A., Elamin, A., Mohamed, S., Yousif, I., Don, J. et al. (2021). Systematic review of glucagon like peptide one receptor agonist liraglutide for subjects with heart failure with reduced left ventricular ejection fraction. Current Diabetes Reviews, 17(3), 280-292. https://doi.org/10.2174/1573399816999200821164129Yi, H.A., Fochtman, B. C., Rizzo, R. C., Jacobs, A. (2016). Inhibition of HIV entry by targeting the envelope transmembrane subunit gp41. Current HIV Research, 14(3), 283-294. https://doi.org/10.2174/1570162x14999160224103908Yi, H.A., Fochtman, B. C., Rizzo, R. C., Jacobs, A. (2016). Inhibition of HIV entry by targeting the envelope transmembrane subunit gp41. Current HIV Research, 14(3), 283-294. https://doi.org/10.2174/1570162x14999160224103908Steward-Tharp, S. M., Song, Y.-J., Siegel, R. M., O'Shea, J. J. (2010). New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression. Annals of the New York Academy of Sciences, 1183(1), 123-148. https://doi.org/10.1111/j.1749-6632.2009.05124.xSteward-Tharp, S. M., Song, Y.-J., Siegel, R. M., O'Shea, J. J. (2010). New insights into T cell biology and T cell-directed therapy for autoimmunity, inflammation, and immunosuppression. Annals of the New York Academy of Sciences, 1183(1), 123-148. https://doi.org/10.1111/j.1749-6632.2009.05124.x

The authors declare that there are no conflicts of interest present.