Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria
An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N'-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Marine drugs - 16(2018), 9 vom: 30. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dahiya, Rajiv [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.02.2019 Date Revised 28.09.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/md16090305 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288375394 |
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| 100 | 1 | |a Dahiya, Rajiv |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 04.02.2019 | ||
| 500 | |a Date Revised 28.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N'-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a N-methylation | |
| 650 | 4 | |a Pseudoalteromonas sp. | |
| 650 | 4 | |a Pseudomonas sp. | |
| 650 | 4 | |a macrocyclization | |
| 650 | 4 | |a marine sponge | |
| 650 | 4 | |a pharmacological activity | |
| 650 | 4 | |a solution-phase peptide synthesis | |
| 650 | 4 | |a tetracyclopeptide | |
| 650 | 7 | |a Anthelmintics |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Antifungal Agents |2 NLM | |
| 650 | 7 | |a Dipeptides |2 NLM | |
| 650 | 7 | |a Peptides, Cyclic |2 NLM | |
| 650 | 7 | |a Proline |2 NLM | |
| 650 | 7 | |a 9DLQ4CIU6V |2 NLM | |
| 700 | 1 | |a Kumar, Suresh |e verfasserin |4 aut | |
| 700 | 1 | |a Khokra, Sukhbir Lal |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Sheeba Varghese |e verfasserin |4 aut | |
| 700 | 1 | |a Sutariya, Vijaykumar B |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatia, Deepak |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Ajay |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Shamjeet |e verfasserin |4 aut | |
| 700 | 1 | |a Maharaj, Sandeep |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/md16090305 |3 Volltext |
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