{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:42:00Z","timestamp":1789429320010,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2021-1049"],"award-info":[{"award-number":["075-15-2021-1049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Antimicrobial peptides are generally considered promising drug candidates for combating resistant bacterial infections. However, the selectivity of their action may vary significantly. Natural gomesin, isolated from haemocytes of the tarantula Acanthoscurria gomesiana, demonstrates a broad spectrum of antimicrobial activities, being the most effective against pathogenic fungi. Methods: Here, we searched for variants of natural gomesin-like peptides and produced their recombinant analogs in the bacterial expression system. The antimicrobial activities of the obtained peptides were tested against a panel of bacterial and yeast strains, and their toxicity towards human cells was examined. Results: Most of the new analogs of gomesin have primary structures homologous to that of the natural gomesin; however, they have fewer amino acid residues and post-translational modifications. One of the discovered analogs, the His-rich shorter peptide from the spider Dysdera sylvatica, designated as DsGom, displays antifungal activity comparable with that of natural gomesin. In the process of the structural\u2013functional study of DsGom, it was shown that this analog retains a basic mechanism of action similar to that of natural gomesin. The DsGom analog has a significantly better toxicity profile as compared to gomesin. At the same time, the loss of the first Arg residue reduces, but does not annul, the antifungal activity of DsGom. Moreover, the acidification of the growth medium reduces the loss of the antifungal activity of this analog. Conclusions: The discovered natural gomesin-like peptides display more selective antifungal activities as compared to gomesin. The low cytotoxicity of DsGom, combined with its high antifungal activity and stability, allows us to consider it a promising drug candidate for the treatment of fungal infections, especially those caused by fungi of the Candida genus.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121606","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T03:46:02Z","timestamp":1734407162000},"page":"1606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Natural Gomesin-like Peptides with More Selective Antifungal Activities"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3539-4906","authenticated-orcid":false,"given":"Ilia A.","family":"Bolosov","sequence":"first","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina I.","family":"Finkina","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-2898","authenticated-orcid":false,"given":"Ivan V.","family":"Bogdanov","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-0157","authenticated-orcid":false,"given":"Victoria N.","family":"Safronova","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8448-031X","authenticated-orcid":false,"given":"Pavel V.","family":"Panteleev","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-249X","authenticated-orcid":false,"given":"Tatiana V.","family":"Ovchinnikova","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41564-022-01172-2","article-title":"COVID-19-Associated Fungal Infections","volume":"7","author":"Hoenigl","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1007\/s00018-011-0710-x","article-title":"Multifunctional Cationic Host Defence Peptides and Their Clinical Applications","volume":"68","author":"Yeung","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.coph.2006.04.006","article-title":"Antibacterial Peptides for Therapeutic Use: Obstacles and Realistic Outlook","volume":"6","author":"Marr","year":"2006","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33464","DOI":"10.1074\/jbc.M001491200","article-title":"Isolation and Characterization of Gomesin, an 18-Residue Cysteine-Rich Defense Peptide from the Spider Acanthoscurria gomesiana Hemocytes with Sequence Similarities to Horseshoe Crab Antimicrobial Peptides of the Tachyplesin Family","volume":"275","author":"Silva","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1021\/acschembio.7b00459","article-title":"Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties","volume":"12","author":"Lawrence","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.exppara.2007.01.022","article-title":"Effect of the Antimicrobial Peptide Gomesin against Different Life Stages of Plasmodium spp","volume":"116","author":"Moreira","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11077","DOI":"10.1021\/la100662a","article-title":"Revealing the Lytic Mechanism of the Antimicrobial Peptide Gomesin by Observing Giant Unilamellar Vesicles","volume":"26","author":"Domingues","year":"2010","journal-title":"Langmuir"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8609","DOI":"10.1021\/la401596s","article-title":"Interaction of the Antimicrobial Peptide Gomesin with Model Membranes: A Calorimetric Study","volume":"29","author":"Domingues","year":"2013","journal-title":"Langmuir"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/bip.20396","article-title":"Structure\u2013Activity Relationship Studies of Gomesin: Importance of the Disulfide Bridges for Conformation, Bioactivities, and Serum Stability","volume":"84","author":"Oliveira","year":"2006","journal-title":"Pept. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/psc.2439","article-title":"Synthesis and Properties of Cyclic Gomesin and Analogues","volume":"18","author":"Machado","year":"2012","journal-title":"J. Pept. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbamem.2006.08.016","article-title":"Conformational and Functional Studies of Gomesin Analogues by CD, EPR and Fluorescence Spectroscopies","volume":"1768","author":"Moraes","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rossi, D.C., Mu\u00f1oz, J.E., Carvalho, D.D., Belmonte, R., Faintuch, B., Borelli, P., Miranda, A., Taborda, C.P., and Daffre, S. (2012). Therapeutic Use of a Cationic Antimicrobial Peptide from the Spider Acanthoscurria gomesianain the Control of Experimental Candidiasis. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-28"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Benfield, A.H., Defaus, S., Lawrence, N., Chaousis, S., Condon, N., Cheneval, O., Huang, Y.-H., Chan, L.Y., Andreu, D., and Craik, D.J. (2021). Cyclic Gomesin, a Stable Redesigned Spider Peptide Able to Enter Cancer Cells. Biochim. Biophys. Acta (BBA) Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2020.183480"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/cbic.201300034","article-title":"Cyclization of the Antimicrobial Peptide Gomesin with Native Chemical Ligation: Influences on Stability and Bioactivity","volume":"14","author":"Chan","year":"2013","journal-title":"ChemBioChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/psc.2843","article-title":"Bioengineering and Functional Characterization of Arenicin Shortened Analogs with Enhanced Antibacterial Activity and Cell Selectivity","volume":"22","author":"Panteleev","year":"2016","journal-title":"J. Pept. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Panteleev, P.V., Bolosov, I.A., Kalashnikov, A.\u00c0., Kokryakov, V.N., Shamova, O.V., Emelianova, A.A., Balandin, S.V., and Ovchinnikova, T.V. (2018). Combined Antibacterial Effects of Goat Cathelicidins with Different Mechanisms of Action. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02983"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Panteleev, P.V., Safronova, V.N., Duan, S., Komlev, A.S., Bolosov, I.A., Kruglikov, R.N., Kombarova, T.I., Korobova, O.V., Pereskokova, E.S., and Borzilov, A.I. (2023). Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm Heteromastus filiformis: Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential. Mar. Drugs, 21.","DOI":"10.3390\/md21120639"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Antoshina, D.V., Balandin, S.V., Finkina, E.I., Bogdanov, I.V., Eremchuk, S.I., Kononova, D.V., Kovrizhnykh, A.A., and Ovchinnikova, T.V. (2024). Acidocin A and Acidocin 8912 Belong to a Distinct Subfamily of Class II Bacteriocins with a Broad Spectrum of Antimicrobial Activity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810059"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41420-018-0030-0","article-title":"Gomesin Peptides Prevent Proliferation and Lead to the Cell Death of Devil Facial Tumour Disease Cells","volume":"4","author":"Deplazes","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.peptides.2012.09.020","article-title":"Expression Systems for Heterologous Production of Antimicrobial Peptides","volume":"38","author":"Parachin","year":"2012","journal-title":"Peptides"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1515\/BC.2008.111","article-title":"Glutaminyl Cyclases from Animals and Plants: A Case of Functionally Convergent Protein Evolution","volume":"389","author":"Schilling","year":"2008","journal-title":"Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Safronova, V.N., Panteleev, P.V., Sukhanov, S.V., Toropygin, I.Y., Bolosov, I.A., and Ovchinnikova, T.V. (2022). Mechanism of Action and Therapeutic Potential of the \u03b2-Hairpin Antimicrobial Peptide Capitellacin from the Marine Polychaeta Capitella teleta. Mar. Drugs, 20.","DOI":"10.3390\/md20030167"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/bip.20660","article-title":"Biological and Structural Characterization of New Linear Gomesin Analogues with Improved Therapeutic Indices","volume":"88","author":"Jouvensal","year":"2007","journal-title":"Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.2174\/0929867324666170424124416","article-title":"A Therapeutic Potential of Animal \u03b2-Hairpin Antimicrobial Peptides","volume":"24","author":"Panteleev","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1021\/ja108943n","article-title":"Protonation, Tautomerization, and Rotameric Structure of Histidine: A Comprehensive Study by Magic-Angle-Spinning Solid-State NMR","volume":"133","author":"Li","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"O\u2019Hanlon, D.E., Moench, T.R., and Cone, R.A. (2013). Vaginal pH and Microbicidal Lactic Acid When Lactobacilli Dominate the Microbiota. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080074"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/12\/1606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:53:31Z","timestamp":1760115211000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/12\/1606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,17]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["pharmaceutics16121606"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16121606","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,17]]}}}