Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic inte...
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2019-12-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.15.286 |
| _version_ | 1818724202109206528 |
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| author | David C. B. Siebert Roman Sommer Domen Pogorevc Michael Hoffmann Silke C. Wenzel Rolf Müller Alexander Titz |
| author_facet | David C. B. Siebert Roman Sommer Domen Pogorevc Michael Hoffmann Silke C. Wenzel Rolf Müller Alexander Titz |
| author_sort | David C. B. Siebert |
| collection | DOAJ |
| description | The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence ᴅ-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide. |
| first_indexed | 2024-12-17T21:22:40Z |
| format | Article |
| id | doaj.art-7b6c682e0adb4e48a02cbe71b43e090e |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-17T21:22:40Z |
| publishDate | 2019-12-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-7b6c682e0adb4e48a02cbe71b43e090e2022-12-21T21:32:08ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972019-12-011512922292910.3762/bjoc.15.2861860-5397-15-286Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesisDavid C. B. Siebert0Roman Sommer1Domen Pogorevc2Michael Hoffmann3Silke C. Wenzel4Rolf Müller5Alexander Titz6Chemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), D-66123 Saarbrücken, GermanyChemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), D-66123 Saarbrücken, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Standort Hannover-Braunschweig, GermanyChemical Biology of Carbohydrates, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), D-66123 Saarbrücken, GermanyThe argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence ᴅ-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide.https://doi.org/10.3762/bjoc.15.286antibioticargyrinmutasynthesisnrpspeptide synthesis |
| spellingShingle | David C. B. Siebert Roman Sommer Domen Pogorevc Michael Hoffmann Silke C. Wenzel Rolf Müller Alexander Titz Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis Beilstein Journal of Organic Chemistry antibiotic argyrin mutasynthesis nrps peptide synthesis |
| title | Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| title_full | Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| title_fullStr | Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| title_full_unstemmed | Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| title_short | Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| title_sort | chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis |
| topic | antibiotic argyrin mutasynthesis nrps peptide synthesis |
| url | https://doi.org/10.3762/bjoc.15.286 |
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