Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12
Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicat...
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2025-04-01
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| author | Malgorzata Anna Paduszynska Damian Neubauer Wojciech Kamysz Elzbieta Kamysz |
| author_facet | Malgorzata Anna Paduszynska Damian Neubauer Wojciech Kamysz Elzbieta Kamysz |
| author_sort | Malgorzata Anna Paduszynska |
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| description | Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH<sub>2</sub>, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the <i>Candida albicans</i>, <i>C. glabrata</i>, <i>C. tropicalis</i> and <i>C. lipolytica</i>. Five compounds: C<sub>10</sub>-KR12-NH<sub>2</sub>, C<sub>12</sub>-KR12-NH<sub>2</sub>, C<sub>14</sub>-KR12-NH<sub>2</sub>, 2-butyloctanoic acid-KR12-NH<sub>2</sub>, and 4-phenylbenzoic acid-KR12-NH<sub>2</sub> were highly active against planktonic cells. C<sub>14</sub>-KR12-NH<sub>2</sub> demonstrated also activity against <i>C. albicans</i> biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH<sub>2</sub> peptide. |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| series | Molecules |
| spelling | doaj-art-dd8f87a0eeb54d159d31d9a0ec4c1df72025-08-20T02:15:58ZengMDPI AGMolecules1420-30492025-04-01307159810.3390/molecules30071598Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12Malgorzata Anna Paduszynska0Damian Neubauer1Wojciech Kamysz2Elzbieta Kamysz3Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, PolandDepartment of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, PolandDepartment of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, PolandLaboratory of Chemistry of Biological Macromolecules, Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, 80-308 Gdansk, PolandCandidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH<sub>2</sub>, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the <i>Candida albicans</i>, <i>C. glabrata</i>, <i>C. tropicalis</i> and <i>C. lipolytica</i>. Five compounds: C<sub>10</sub>-KR12-NH<sub>2</sub>, C<sub>12</sub>-KR12-NH<sub>2</sub>, C<sub>14</sub>-KR12-NH<sub>2</sub>, 2-butyloctanoic acid-KR12-NH<sub>2</sub>, and 4-phenylbenzoic acid-KR12-NH<sub>2</sub> were highly active against planktonic cells. C<sub>14</sub>-KR12-NH<sub>2</sub> demonstrated also activity against <i>C. albicans</i> biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH<sub>2</sub> peptide.https://www.mdpi.com/1420-3049/30/7/1598lipopeptidesantimicrobial peptidesKR-12LL-37fungal biofilm<i>Candida</i> |
| spellingShingle | Malgorzata Anna Paduszynska Damian Neubauer Wojciech Kamysz Elzbieta Kamysz Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 Molecules lipopeptides antimicrobial peptides KR-12 LL-37 fungal biofilm <i>Candida</i> |
| title | Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 |
| title_full | Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 |
| title_fullStr | Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 |
| title_full_unstemmed | Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 |
| title_short | Anticandidal Activity of Lipopeptides Containing an LL-37-Derived Peptide Fragment KR12 |
| title_sort | anticandidal activity of lipopeptides containing an ll 37 derived peptide fragment kr12 |
| topic | lipopeptides antimicrobial peptides KR-12 LL-37 fungal biofilm <i>Candida</i> |
| url | https://www.mdpi.com/1420-3049/30/7/1598 |
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