Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids
Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality ag...
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2025-05-01
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| author | Nora Angelova Ivan Iliev Veronica Nemska Tatyana Dzimbova Nelly Georgieva Dancho Danalev Emilia Naydenova |
| author_facet | Nora Angelova Ivan Iliev Veronica Nemska Tatyana Dzimbova Nelly Georgieva Dancho Danalev Emilia Naydenova |
| author_sort | Nora Angelova |
| collection | DOAJ |
| description | Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality against bacterial and cancer cells. The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of new analogs of aurein 1.2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. The antibacterial activity was estimated against Gram-positive and Gram-negative bacteria using broth microdilution method in concentrations from 0 to 320 µg/mL to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The antiproliferative activity test shows that the peptide analog EH [Orn]<sup>8</sup> has the highest activity (IC<sub>50</sub> = 44 ± 38 μM) for the three cell lines studied (MCF-12F, MCF-7, and MDA-MB-231). The same compound exhibited good antimicrobial activity. The obtained results reveal that replacement of Lys with non-proteinogenic amino acids can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development. |
| format | Article |
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| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-bdcf34d2488e4afcaf6bd1fd93b616602025-08-20T01:49:14ZengMDPI AGMolecules1420-30492025-05-01309205010.3390/molecules30092050Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino AcidsNora Angelova0Ivan Iliev1Veronica Nemska2Tatyana Dzimbova3Nelly Georgieva4Dancho Danalev5Emilia Naydenova6Department of Organic Chemistry, University of Chemical Technology and Metallurgy, 1797 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, 1113 Sofia, BulgariaDepartment of Biotechnology, University of Chemical Technology and Metallurgy, 1797 Sofia, BulgariaDepartment Sport, Faculty of Public Health, Health Care and Sport, South-West University “Neofit Rilski”, 2700 Blagoevgrad, BulgariaDepartment of Biotechnology, University of Chemical Technology and Metallurgy, 1797 Sofia, BulgariaDepartment of Biotechnology, University of Chemical Technology and Metallurgy, 1797 Sofia, BulgariaDepartment of Organic Chemistry, University of Chemical Technology and Metallurgy, 1797 Sofia, BulgariaExtensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality against bacterial and cancer cells. The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of new analogs of aurein 1.2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. The antibacterial activity was estimated against Gram-positive and Gram-negative bacteria using broth microdilution method in concentrations from 0 to 320 µg/mL to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The antiproliferative activity test shows that the peptide analog EH [Orn]<sup>8</sup> has the highest activity (IC<sub>50</sub> = 44 ± 38 μM) for the three cell lines studied (MCF-12F, MCF-7, and MDA-MB-231). The same compound exhibited good antimicrobial activity. The obtained results reveal that replacement of Lys with non-proteinogenic amino acids can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development.https://www.mdpi.com/1420-3049/30/9/2050antimicrobial peptides (AMPs)aurein 1.2antimicrobial activityantiproliferative activitynonproteinogenic amino acidssecondary structure prediction |
| spellingShingle | Nora Angelova Ivan Iliev Veronica Nemska Tatyana Dzimbova Nelly Georgieva Dancho Danalev Emilia Naydenova Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids Molecules antimicrobial peptides (AMPs) aurein 1.2 antimicrobial activity antiproliferative activity nonproteinogenic amino acids secondary structure prediction |
| title | Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids |
| title_full | Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids |
| title_fullStr | Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids |
| title_full_unstemmed | Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids |
| title_short | Design, Synthesis, and Biological Evaluation of New Analogs of Aurein 1.2 Containing Non-Proteinogenic Amino Acids |
| title_sort | design synthesis and biological evaluation of new analogs of aurein 1 2 containing non proteinogenic amino acids |
| topic | antimicrobial peptides (AMPs) aurein 1.2 antimicrobial activity antiproliferative activity nonproteinogenic amino acids secondary structure prediction |
| url | https://www.mdpi.com/1420-3049/30/9/2050 |
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