ЭВОЛЮЦИОННОЕ РАЗВИТИЕ И СТРУКТУРНОЕ РАЗНООБРАЗИЕ ПРИРОДНЫХ АНТИМИКРОБНЫХ ПЕПТИДОВ, ПЕПТИДОМИМЕТИКОВ И КАТИОННЫХ АМФИФИЛОВ НА ОСНОВЕ АМИНОКИСЛОТ
Аннотация
В обзорной статье прослеживаются основные тенденции синтетического подхода к решению вопроса преодоления резистентности патогенных штаммов бактерий. Приведены основные стратегии поиска перспективных агентов, начиная с природных антимикробных пептидов или пептидов «защиты человека», с последующим эволюционным переходом к синтетическим пептидомиметикам макромолекулярного или олигомерного типов, а также подхода, основанного на мембранно-активных низкомолекулярных катионных амфифилах. Показано структурное многообразие пептидомиметиков с высокой бактерицидной активностью, обладающих повышенной устойчивостью к действию протеолитических ферментов по сравнению с природными пептидами. Большое внимание уделено различным алифатическим и ароматическим катионным амфифилам на основе аминокислот. Отмечены потенциальные возможности этого класса соединений в качестве антимикробных агентов. Амфифильная структура синтезированных соединений позволяет им избирательно воздействовать на бактериальные мембраны и не приводит к запуску у бактерий процесса развития резистентности.
Литература
Tacconelli, E., Magrini, N., Kahlmeter, G., and Singh, N. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics // World Health Organization. 2017. V. 27. P. 318–327.
Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Carmeli, Y. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis. 2018. V. 18. P. 318–327. doi: 10.1016/s1473-3099(17)30753-3.
Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States. Atlanta, GA: US Department of Health and Human Services, CDC. 2019. doi: 10.15620/cdc:82532.
Cerceo E., Deitelzweig S. B., Sherman B. M., Amin A. N. Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options. Microb. Drug. Resist. 2016. V. 22. P. 412–431. doi: 10.1089/mdr.2015.0220.
Wang G. Database-guided discovery of potent peptides to combat HIV-1 or superbugs. Pharmaceuticals. 2013. V. 6. P. 728–758. doi: 10.3390/ph6060728.
De Oliveira D. M., Forde B. M., Kidd T. J., Harris P. N., Schembri M. A., Beatson S. A., Walker M. J. Antimicrobial Resistance in ESKAPE Pathogens. 2020. Clin. Microbiol. Rev. 2020. V. 33. P. 1–49. doi: 10.1128/CMR.00181-19.
Santajit S., Indrawattana N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed Res. Int. 2016. V. 2016. P. 1–8. doi: 10.1155/2016/2475067.
Tincho M. B., Morris T., Meyer M., and Pretorius A. Antibacterial Activity of Rationally Designed Antimicrobial Peptides. Int. J. Microbiol. 2020. V. 2020. P. 1–9. doi: 10.1155/2020/2131535.
Giuliani A., Rinaldi A. C. Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell. Mol. Life Sci. 2011. V. 68. P. 2255–2266. doi: 10.1007/s00018-011-0717-3.
Amerikova M., Pencheva El-Tibi I., Maslarska V., Bozhanov S., Tachkov K. Antimicrobial activity, mechanism of action, and methods for stabilisation of defensins as new therapeutic agents. Biotechnol. Biotechnolog. Equip. 2019. V. 33. P. 671–682. doi: 10.1080/13102818.2019.1611385.
Seyfi R., Kahaki F. A., Ebrahimi T., Montazersaheb S., Eyvazi S., Babaeipour V., Tarhriz V. Antimicrobial Peptides (AMPs): Roles, Functions and Mechanism of Action. Int. J. Pept. Res. Ther. 2019. V. 26. P. 1451–1463. doi: 10.1007/s10989-019-09946-9.
Bechinger B., Gorr S.-U. Antimicrobial Peptides: Mechanisms of Action and Resistance. J. Dent. Res. 2016. V. 96. P. 254–260. doi: 10.1177/0022034516679973.
Molchanova N., Hansen P.R., Franzyk H. Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs. Molecules. 2017. V. 22. P. 1430. doi: 10.3390/molecules22091430.
Ghosh C., Haldar J. Membrane-Active Small Molecules: Designs Inspired by Antimicrobial Peptides. ChemMedChem. .2015. V. 10. P. 1606–1624. doi: 10.1002/cmdc.201500299.
Мусин Х.Г. Антимикробные пептиды — потенциальная замена традиционным антибиотикам. Инфекция и иммунитет. V. 8. P. 295–308. doi: 10.15789/2220-7619-2018-3-295-308.
Koehbach J. and Craik D. J. The Vast Structural Diversity of Antimicrobial Peptides. Trends Pharmacol. Sci. 2019. V. 40. P. 517–528. doi: 10.1016/j.tips.2019.04.012.
Singh P., Hockenberry A. J., Tiruvadi V. R., Meaney D. F. Computational investigation of the changing patterns of subtype specific NMDA receptor activation during physiological glutamatergic neurotransmission. PLoS Comput. Biol. 2011. V. 7. P. 1-17. doi: 10.1371/journal.pcbi.1002106.
Denieva Z. G., Romanova N. A., Bodrova T. G., Budanova U. A., Sebyakin Y. L. Synthesis of Amphiphilic Peptidomimetics Based on the Aliphatic Derivatives of Natural Amino Acids. Moscow Univ. Chem. Bull. V. 74. P. 300–305. doi: 10.3103/s0027131419060087.
Kumar P., Kizhakkedathu J. N., Straus S. K. Antimicrobial peptides: diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules. 2018. V. 8. P. 1–24. doi: 10.3390/biom8010004.
Raheem N., Straus S. K. Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions. Front. Microbio. 2019. V. 10. P. 1–14. doi: 10.3389/fmicb.2019.02866.
Mojsoska B., Jenssen H. Peptides and peptidomimetics for antimicrobial drug design. Pharmaceuticals. V. 8. P. 366–415. doi: 10.3390/ph8030366.
Qvit N., Rubin S.J.S., Urban T.J., Mochly-Rosen D., Gross E.R. Peptidomimetic therapeutics: scientific approaches and opportunities. Drug Discov. Today. 2017. V. 22. P. 454–462. doi: 10.1016/j.drudis.2016.11.003.
Dias C., Rauter A.P. Membrane-targeting antibiotics: recent developments outside the peptide space. Fut. Med. Chem. 2019. V. 11. P. 211–228. doi: 10.4155/fmc-2018-0254.
Kuroda K., Caputo G. A. Antimicrobial polymers as synthetic mimics of host-defense peptides. Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol. 2013. V. 5. P. 49–66. doi: 10.1002/wnan.1199.
Uppu D. S., Akkapeddi P., Manjunath G. B., Yarlagadda V., Hoque J., Haldar J. Polymers with tunable side-chain amphiphilicity as non-hemolytic antibacterial agents. Chem. Commun. 2013. V. 49. P. 9389–9391. doi: 10.1039/C3CC43751E.
Engler A. C., Wiradharma N., Ong Z. Y., Coady D. J., Hedrick J. L., Yang Y. Y. Emerging trends in macromolecular antimicrobials to fight multi-drug-resistant infections. Nano Today. 2012. V. 7. P. 201–222. doi: 10.1016/j.nantod.2012.04.003.
Nadithe V., Liu R., Killinger B. A., Movassaghian S., Kim N. H., Moszczynska A. B., and Merkel O. M. Screening nylon-3 polymers, a new class of cationic amphiphiles, for siRNA delivery. Mol. Pharm. 2015. V. 12. P. 362–374. doi: 10.1021/mp5004724.
Liu R., Chen X., Falk S. P., Mowery B. P., Karlsson A. J., Weisblum B., and Gellman S. H. Structure–activity relationships among antifungal nylon-3 polymers: identification of materials active against drug-resistant strains of Candida albicans. J. Am. Chem. Soc. 2014. V. 136. P. 4333–4342. doi: 10.1021/ja500036r.
Chen Y., Mant C. T., Farmer S. W., Hancock R. E., Vasil M. L., and Hodges R. S. Rational design of α-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J. Boil. Chem. 2005. P. 280. P. 12316–12329. doi: 10.1074/jbc.M413406200.
Violette A., Averlant-Petit M. C., Semetey V., Hemmerlin C., Casimir R., Graff R., Guichard G. N, N‘-Linked Oligoureas as Foldamers: Chain Length Requirements for Helix Formation in Protic Solvent Investigated by Circular Dichroism, NMR Spectroscopy, and Molecular Dynamics. J. Am. Chem. Soc. 2005. V. 127. P. 2156–2164. doi: 10.1021/ja044392b.
Chongsiriwatana N. P., Patch J. A., Czyzewski A. M., Dohm M. T., Ivankin A., Gidalevitz D., and Barron A. E. Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides. Proc. Natl. Acad. Sci. 2008. V. 105. P. 2794–2799. doi: 10.1073/pnas.0708254105.
Себякин Ю.Л., Лосева А.А., Буданова У.А., Любешкин А.В. Синтез дипептидного и углеводного производных ивермектина В1. Макрогетероциклы. 2016. V. 9. P. 314–319. doi: 10.6060/mhc160644s.
Radzishevsky I. S., Rotem S., Bourdetsky D., Navon-Venezia S., Carmeli Y., and Mor A. Improved antimicrobial peptides based on acyl-lysine oligomers. Nat. Biotechnol. 2007. V. 25. 657–659. doi: 10.1038/nbt1309.
Padhee S., Hu Y., Niu Y., Bai G., Wu H., Costanza F., and Cai J. Non-hemolytic α-AApeptides as antimicrobial peptidomimetics. Chem. Commun. 2011. V. 47. P. 9729–9731. doi: 10.1039/C1CC13684D.
Lienkamp, K., Madkour, A. E., and Tew, G. N. (2010) Antibacterial peptidomimetics: polymeric synthetic mimics of antimicrobial peptides, Polymer composites–polyolefin fractionation–polymeric peptidomimetics–collagens, 251, 141–172, doi: 10.1007/12_2010_85.
Meir, O., Zaknoon, F., Cogan, U., and Mor, A. (2017) A broad-spectrum bactericidal lipopeptide with anti-biofilm properties, Sci. Rep., 7, 1–11, doi: 10.1038/s41598-017-02373-0.
Singh, S., Wang, M., Gao, R., Teng, P., Odom, T., Zhang, E., and Cai, J. (2020) Lipidated α/Sulfono-α-AA heterogeneous peptides as antimicrobial agents for MRSA, Bioorg. Med. Chem., 28, 115241, doi: 10.1016/j.bmc.2019.115241.
Mahlapuu, M., Björn, C., and Ekblom, J. (2020) Antimicrobial peptides as therapeutic agents: opportunities and challenges, Crit. Rev. Biotechnol., 40, 978–992, doi: 10.1080/07388551.2020.1796576.
Kundu, R. (2020) Cationic amphiphilic peptide: A nature-inspired synthetic antimicrobial peptide, ChemMedChem, 15, 1887–1896, doi: 10.1002/cmdc.202000301.
Wang, M., Gao, R., Sang, P., Odom, T., Zheng, M., Shi, Y., Cai, J. (2020) Dimeric γ-AA peptides With Potent and Selective Antibacterial Activity, Front. Chem., 8, 1–11, doi: 10.3389/fchem.2020.00441.
Oliva, R., Chino, M., Pane, K., Pistorio, V., De Santis, A., Pizzo, E., Petraccone, L. (2018) Exploring the role of unnatural amino acids in antimicrobial peptides, Sci. Rep., 8, 1–16, doi: 10.1038/s41598-018-27231-5.
Окороченков, С. А., Желтухина, Г. А., Небольсин, В. Е. (2012) Антимикробные пептиды: механизмы действия и перспективы практического применения, Биомедицинская химия, 58, 131–143, doi: 10.18097/pbmc20125802131.
Филатова С.М., Дениева З.Г., Буданова У.А., Себякин Ю.Л. (2020) Синтез низкомолекулярных антибактериальных пептидных миметиков на основе диалкил- и диациламинов, Вестн. Моск. Ун-та. Сер. 2. Химия, 61, 405–413.
Marusova (Soloveva) V.V., Zagitova R.I., Budanova U.A., Sebyakin Y.L. Multifunctional ipoamino acid derivatives with potential biological activity. Moscow Univ. Chem. Bull. 2018. V. 73. P. 74–79. doi: 10.3103/S0027131418020098.
Shahzadi I., Jalil A., Asim M. H., Hupfauf A., Gust R., Nelles P. A., Bernkop-Schnürch A. Lipophilic arginine esters: The gateway to preservatives without side effects. Mol. Pharmaceutics. 2020. V. 17. P. 3129–3139. doi: 10.1021/acs.molpharmaceut.0c00610.
Mahindra A., Sharma K. K., Rathore D., Khan S. I., Jacob M. R., and Jain R. Synthesis and antimicrobial activities of His (2-aryl)-Arg and Trp-His (2-aryl) classes of dipeptidomimetics. MedChemComm. 2014. V. 5. P. 671–676. doi: 10.1039/C4MD00041B.
Lohan S., Monga J., Chauhan C. S., and Bisht G. S. In vitro and in vivo evaluation of small cationic abiotic lipopeptides as novel antifungal agents. Chem. Bio. Drug Des. 2015. V. 86. P. 829–836. doi: 10.1111/cbdd.12558.
Armas F., Pacor S., Ferrari E., Guida F., Pertinhez T. A., Romani A. A., and Benincasa M. Design, antimicrobial activity and mechanism of action of Arg-rich ultra-short cationic lipopeptides. PloS One. 2019. V. 14, 1–22, doi: 10.1371/journal.pone.0212447.
Hoque J., Konai M. M., Sequeira S. S., Samaddar S., and Haldar J. Antibacterial and antibiofilm activity of cationic small molecules with spatial positioning of hydrophobicity: an in vitro and in vivo evaluation. J. Med. Chem. 2016. V. 59. 10750–10762. doi: 10.1021/acs.jmedchem.6b01435.
Edwards-Gayle C. J., Castelletto V., Hamley I. W., Barrett G., Greco F., Hermida-Merino D., and Ruokolainen J. Self-Assembly, Antimicrobial Activity, and Membrane Interactions of Arginine-Capped Peptide Bola-Amphiphiles. ACS Appl. Bio Mater. 2019. V. 2. P. 2208–2218. doi: 10.1021/acsabm.9b00172.
Hegarty J., Krzeminski J., Sharma A., Guzman-Villanueva D., Weissig V., and Stewart D. Bolaamphiphile-based nanocomplex delivery of phosphorothioate gapmer antisense oligonucleotides as a treatment for Clostridium difficile. Int. J. Nanomedicine. 2016. V. 11. P. 3607–3619. doi: 10.2147/IJN.S109600.
Hegarty J. P., and Stewart D. B. Advances in therapeutic bacterial antisense biotechnology. Appl. Microbiol. Biotechnol. 2018. V. 102. P. 1055–1065. doi: 10.1007/s00253-017-8671-0.
Гостенин В.Б., Щелик И.С., Себякин Ю.Л. Синтез и оптимизация процесса получения октавалентного болаамфифила с терминальными остатками d-маннозы. Тонкие химические технологии. 2015. V. 10. P. 39–43.
LaDow J. E., Warnock D. C., Hamill K. M., Simmons K. L., Davis R. W., Schwantes C. R., and Minbiole K. P. Bicephalic amphiphile architecture affects antibacterial activity. Eur. J. Med. Chem. 2011. V. 46. P. 4219–4226. doi: 10.1016/j.ejmech.2011.06.026.
Konai M. M., and Haldar J. Lysine-based small molecules that disrupt biofilms and kill both actively growing planktonic and nondividing stationary phase bacteria. ACS Infect. Dis. 2015. V. 1. P. 469–478. doi: 10.1021/acsinfecdis.5b00056.
Konai M. M., and Haldar J. Lysine-Based Small Molecule Sensitizes Rifampicin and Tetracycline against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa. ACS Infect. Dis. 2019. V. 6. P. 91–99. doi: 10.1021/acsinfecdis.9b00221.
Boullet H., Bentot F., Hequet A., Ganem-Elbaz C., Bechara C., Pacreau E., and Moumné R. Small antiMicrobial peptide with in vivo activity against sepsis. Molecules. 2019. V. 24. P. 1702. doi: 10.3390/molecules24091702.
Zhang E., Bai P. Y., Cui D. Y., Chu W. C., Hua Y. G., Liu Q., and Liu H. M. Synthesis and bioactivities study of new antibacterial peptide mimics: The dialkyl cationic amphiphiles. Eur. J. Med. Chem. 2018. V. 143. P. 1489–1509. doi: 10.1016/j.ejmech.2017.10.044.
Liu F., Yang L., Li Y., Junier A., Ma F., Chen J., and Sang H. In Vitro and In Vivo Study of Amphotericin B Formulation with Quaternized Bioreducible Lipidoids. ACS Biomater. Sci. Eng. 2020. V. 6. P. 1064–1073. doi: 10.1021/acsbiomaterials.9b01722.
Faig A., Arthur T. D., Fitzgerald P. O., Chikindas M., Mintzer E., and Uhrich K. E. Biscationic Tartaric Acid-Based Amphiphiles: Charge Location Impacts Antimicrobial Activity. Langmuir. 2015. V. 31. P. 11875–11885. doi: 10.1021/acs.langmuir.5b03347.
Zhang, Y., Algburi, A., Wang, N., Kholodovych, V., Oh, D. O., Chikindas, M., and Uhrich, K. E. (2017) Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state, Nanomedicine: NBM, 13, 343–352, doi: 10.1016/j.nano.2016.07.018.
Gadhave A. Determination of hydrophilic-lipophilic balance value. 2014. Int. J. Sci. Res. V. 3. P. 573–575.
Konai M. M., Ghosh C., Yarlagadda V., Samaddar S., and Haldar J. Membrane active phenylalanine conjugated lipophilic norspermidine derivatives with selective antibacterial activity. J. Med. Chem. 2014. V. 57. P. 9409–9423. doi: 10.1021/jm5013566.
Kuppusamy R., Yasir M., Berry T., Cranfield C. G., Nizalapur S., Yee E., Kumar N. Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents. Eur. J. Med. Chem. V. 143. P. 1702–1722. doi: 10.1016/j.ejmech.2017.10.066.
Murugan R. N., Jacob B., Ahn M., Hwang E., Sohn H., Park H. N., Hyun J. K. De novo design and synthesis of ultra-short peptidomimetic antibiotics having dual antimicrobial and anti-inflammatory activities. PloS one. 2013. V. 8. P. 1–15. doi: 10.1371/journal.pone.0080025.
Teng P., Huo D., Nimmagadda A., Wu J., She F., Su M., and Hu Y. Small antimicrobial agents based on acylated reduced amide scaffold. Eur. J. Med. Chem. 2016. V. 59. P. 7877–7887. doi: 10.1021/acs.jmedchem.6b00640.
Bucki R., Niemirowicz K., Wnorowska U., Byfield F. J., Piktel E., Wątek M., Savage P. B. Bactericidal activity of ceragenin CSA-13 in cell culture and in an animal model of peritoneal infection. Antimicrob. Agents Chemother. 2015. V. 59. P. 6274–6282. doi: 10.1128/AAC.00653-15.
Divakara S. S. M. L-Lysine based lipidated biphenyls as agents with anti-biofilm and anti-inflammatory properties that also inhibit intracellular bacteria. Chem. Commun. 2017. V. 53. P. 8427–8430. doi: 10.1039/C7CC04206J.
Zhou M., Zheng M., Cai J. Small Molecules with Membrane-Active Antibacterial Activity. ACS Appl. Mater. Interfaces. 2020. V. 12. P. 21292–21299. doi: 10.1021/acsami.9b20161.
Isaksson J., Brandsdal B.O., Engqvist M., Flaten G.E., Svendsen J.S., Stensen W. A synthetic antimicrobial peptidomimetic (LTX 109): stereochemical impact on membrane disruption. J. Med. Chem. 2011. V. 54. P. 5786–5795. doi: 10.1021/jm200450h.
Niu Y., Wang M., Cao Y., Nimmagadda A., Hu J., Wu Y., Ye X.-S. Rational Design of Dimeric Lysine N-Alkylamides as Potent and Broad-Spectrum Antibacterial Agents. J. Med. Chem. 2018. V. 61. P. 2865–2874. doi: 10.1021/acs.jmedchem.7b01704.
Ghosh C., Manjunath G. B., Konai M. M., Uppu D. S. S. M., Paramanandham K., Shome B. R., Haldar J. Aryl-alkyl-lysines: Membrane-Active Small Molecules Active against Murine Model of Burn Infection. ACS Infect. Dis. 2015. V. 2. P. 111–122. doi: 10.1021/acsinfecdis.5b00092.
Ghosh C., Manjunath G. B., Akkapeddi P., Yarlagadda V., Hoque J., Uppu D. S. S. M., Haldar J. Small Molecular Antibacterial Peptoid Mimics: The Simpler the Better! J. Med. Chem. 2014. V. 57. P. 1428–1436. doi: 10.1021/jm401680a.
Ghosh C., Manjunath G. B., Konai M. M., Uppu D. S. S. M., Hoque J., Paramanandham K., Haldar J. Aryl-Alkyl-Lysines: Agents That Kill Planktonic Cells, Persister Cells, Biofilms of MRSA and Protect Mice from Skin-Infection. PLoS One. V. 10. P. 1–19. doi: 10.1371/journal.pone.0144094.
Ghosh C., Harmouche N., Bechinger B., Haldar J. Aryl-Alkyl-Lysines Interact with Anionic Lipid Components of Bacterial Cell Envelope Eliciting Anti-Inflammatory and Antibiofilm Properties. ACS Omega. 2018. V. 3. P. 9182–9190. doi: 10.1021/acsomega.8b01052.