Challenges with the Synthesis of a Macrocyclic Thioether Peptide : From Milligram to Multigram Using Solid Phase Peptide Synthesis (SPPS)
We describe an optimization and scale-up of the 45-membered macrocyclic thioether peptide BMS-986189 utilizing solid-phase peptide synthesis (SPPS). Improvements to linear peptide isolation, macrocyclization, and peptide purification were demonstrated to increase the throughput and purification of material on scale and enabled the synthesis and purification of >60 g of target peptide. Taken together, not only these improvements resulted in a 28-fold yield increase from the original SPPS approach, but also the generality of this newly developed SPPS purification sequence has found application in the synthesis and purification of other macrocyclic thioether peptides.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The Journal of organic chemistry - (2024) vom: 23. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kempson, James [VerfasserIn] |
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Date Revised 23.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1021/acs.joc.4c00429 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371402913 |
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| 100 | 1 | |a Kempson, James |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Challenges with the Synthesis of a Macrocyclic Thioether Peptide |b From Milligram to Multigram Using Solid Phase Peptide Synthesis (SPPS) |
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| 500 | |a Date Revised 23.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a We describe an optimization and scale-up of the 45-membered macrocyclic thioether peptide BMS-986189 utilizing solid-phase peptide synthesis (SPPS). Improvements to linear peptide isolation, macrocyclization, and peptide purification were demonstrated to increase the throughput and purification of material on scale and enabled the synthesis and purification of >60 g of target peptide. Taken together, not only these improvements resulted in a 28-fold yield increase from the original SPPS approach, but also the generality of this newly developed SPPS purification sequence has found application in the synthesis and purification of other macrocyclic thioether peptides | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Zhao, Rulin |e verfasserin |4 aut | |
| 700 | 1 | |a Pawluczyk, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huiping |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Xiaoping |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, Martin P |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Dauh-Rurng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Yip, Shiuhang |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Traeger, Sarah C |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Stella |e verfasserin |4 aut | |
| 700 | 1 | |a Cutrone, Jingfang |e verfasserin |4 aut | |
| 700 | 1 | |a Mukherjee, Subha |e verfasserin |4 aut | |
| 700 | 1 | |a Sfouggatakis, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Poss, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Scola, Paul M |e verfasserin |4 aut | |
| 700 | 1 | |a Meanwell, Nicholas A |e verfasserin |4 aut | |
| 700 | 1 | |a Carter, Percy H |e verfasserin |4 aut | |
| 700 | 1 | |a Mathur, Arvind |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.joc.4c00429 |3 Volltext |
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