1. Scientific and Production Center “Armbiotechnology” NAS RA, Yerevan, Armenia 2. Scientific and Production Center “Armbiotechnology” NAS RA, Yerevan, Armenia; Yerevan State University, Yerevan, Armenia
Currently non-protein amino acids and synthetic peptides are widely used as blocks in drug design. Many proteases are of great interest for pharmacology due to their key role in various pathologies. Bacterial collagenase (EC 3.4.24.3) is quite an attractive target for drug development as the inhibitors of bacterial collagenolytic protease may stop propagation of diseases caused by infections. The interaction of peptides containing unusual amino acids with Clostridium histolyticum collagenase has been evaluated by molecular docking followed by the measurement of enzyme inhibition by selected compounds. According to the docking analysis, 4 compounds were selected and synthesized for further research. Measurement of enzyme activity revealed that all tested compounds inhibited collagenase activity with IC₅₀ values ranging within 1.45–2.08 μM. The antibacterial activity of synthesized compounds against some resistant strains was characterized by MICs values ranging within 4.6–9.2 μg/ml.
Sargsyan A.S., Karapetyan L.T., Mkhitaryan A.V., Stepanyan L.A., Sargsyan T.H., Danghyan Yu.M., Sargsyan A.V., Oganezova G.G., Hovhannisyan N.A. (2024) Modeling, synthesis and in vitro testing of peptides based on unusual amino acids as potential antibacterial agents. Biomeditsinskaya Khimiya, 70(6), 413-420.
Sargsyan A.S. et al. Modeling, synthesis and in vitro testing of peptides based on unusual amino acids as potential antibacterial agents // Biomeditsinskaya Khimiya. - 2024. - V. 70. -N 6. - P. 413-420.
Sargsyan A.S. et al., "Modeling, synthesis and in vitro testing of peptides based on unusual amino acids as potential antibacterial agents." Biomeditsinskaya Khimiya 70.6 (2024): 413-420.
Sargsyan, A. S., Karapetyan, L. T., Mkhitaryan, A. V., Stepanyan, L. A., Sargsyan, T. H., Danghyan, Yu. M., Sargsyan, A. V., Oganezova, G. G., Hovhannisyan, N. A. (2024). Modeling, synthesis and in vitro testing of peptides based on unusual amino acids as potential antibacterial agents. Biomeditsinskaya Khimiya, 70(6), 413-420.
References
Giacomini E., Perrone V., Alessandrini D., Paoli D., Nappi C., Degli Esposti L. (2021) Evidence of antibiotic resistance from population-based studies: A narrative review. Infect. Drug Resist., 14, 849–858. CrossRef Scholar google search
Du Y., Li L., Zheng Y., Liu J., Gong J., Qiu Z., Li Y., Qiao J., Huo Y.X. (2022) Incorporation of non-canonical amino acids into antimicrobial peptides: Advances, challenges, and perspectives. Appl. Environ. Microbiol., 88(23), e0161722. CrossRef Scholar google search
Sargsyan A.S., Babayan B.G., Avetisyan N.S., Mkrtchyan A.G., Hovhannisyan A.M., Hovhannisyan N.A. (2018) Heterocyclic substituted non-protein amino acids as inhibitors of Clostridium histolyticum collagenase. Armenian Biological J., 70(1), 12–15. Scholar google search
Karaman R., Jubeh B., Breijyeh Z. (2020) Resistance of gram-positive bacteria to current antibacterial agents and overcoming approaches. Molecules, 25(12), 2888. CrossRef Scholar google search
Hovhannisyan N., Harutyunyan Sh., Hovhannisyan A., Hambardzumyan A., Chitchyan M., Melkumyan M., Oganezova G., Avetisyan N. (2023) The novel inhibitors of serine proteases. Amino Acids, 37(3), 531–536. CrossRef Scholar google search
Trott O., Olson A.J. (2010) AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 31(2), 455–461. CrossRef Scholar google search
Sargsyan T., Stepanyan L., Israyelyan M., Hakobyan H., Jamgaryan S., Gasparyan A., Saghyan A. (2024) The synthesis and in vitro study of 9-fluorenylmethoxycarbonyl protected non-protein amino acids antimicrobial activity. Eurasian Chem.-Technol. J., 25(4), 235–240. CrossRef Scholar google search
Jolene L.L., Dunn M.K. (2018) Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg. Med. Chem., 26(10), 2700–2707. CrossRef Scholar google search
Bellotto O., Semeraro S., Bandiera A., Tramer F., Pavan N., Marchesan S. (2022) Polymer conjugates of antimicrobial peptides (AMPs) with d-amino acids (d-aa): State of the art and future opportunities. Pharmaceutics, 14(2), 446–465. CrossRef Scholar google search
Wang G., Li X., Wang Z. (2016) APD3: The antimicrobial peptide database as a tool for research and education. Nucleic Acids Res., 44(D1), D1087–D1093. CrossRef Scholar google search
Kerru N., Gummidi L., Maddila S., Gangu K.K., Sreekantha B., Jonnalagadda A. (2020) A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 25(8), 1909–1951. CrossRef Scholar google search
Kumar A., Singh A.K., Singh H., Vijayan V., Kumar D., Naik J., Thareja S., Yadav J.P., Pathak P., Grishina M., Verma A., Khalilullah H., Jaremko M., Emwas A.H., Kumar P. (2023) Nitrogen containing heterocycles as anticancer agents: A medicinal chemistry perspective. Pharmaceuticals, 16(2), 299–367. CrossRef Scholar google search
Sargsyan A., Hakobyan H., Mardiyan Z., Jamharyan S., Dadayan A., Sargsyan T., Hovhannisyan N. (2023) Modeling, synthesis and in vitro screening of unusual amino acids and peptides as protease inhibitors. J. Chem. Technol. Metall., 58(3), 615–620. CrossRef Scholar google search
Eckhard U., Schönauer E., Brandstetter H. (2013) Structural basis for activity regulation and substrate preference of clostridial collagenases G, H, and T. J. Biol. Chem., 288(28), 20184–20194. CrossRef Scholar google search
