Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis
The development of peptide-based pharmaceutics is a hot topic in the pharmaceutical industry and in basic research. However, from the research and development perspective there is an unmet need for new, alternative, solid-phase peptide synthesizers that are highly efficient, automated, robust, able...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | SLAS Technology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2472630323000031 |
| _version_ | 1797854451133841408 |
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| author | Krisztina Kiss Soma Ránky Zsuzsanna Gyulai László Molnár |
| author_facet | Krisztina Kiss Soma Ránky Zsuzsanna Gyulai László Molnár |
| author_sort | Krisztina Kiss |
| collection | DOAJ |
| description | The development of peptide-based pharmaceutics is a hot topic in the pharmaceutical industry and in basic research. However, from the research and development perspective there is an unmet need for new, alternative, solid-phase peptide synthesizers that are highly efficient, automated, robust, able to synthetize peptides in parallel, inexpensive (to obtain and operate), have potential to be scaled up, and even comply with the principles of green chemistry. Moreover, a peptide synthesizer of this type could also fill the gap in university research, and therefore speed the advancement of peptide-based pharmaceutical options. This paper presents a Tecan add-on peptide synthesizer (TaPSy), which has operational flexibility (coupling time: 15–30 min), can handle all manual synthesis methods, and is economical (solvent use: 34.5 mL/cycle, while handling 0.49 mmol scale/reactor, even with ≤3 equivalents of activated amino acid derivatives). Moreover, it can carry out parallel synthesis of up to 12 different peptides (0.49 mmol scale in each). TaPSy uses no heating or high pressure, while it is still resistant to external influences (operating conditions: atmospheric pressure, room temperature 20–40 ˚C, including high [>70%] relative humidity). The system's solvent can also be switched from DMF to a green and biorenewable solvent, γ-valerolactone (GVL), without further adjustment. The designed TaPSy system can produce peptides with high purity (>70%), even with the green GVL solvent alternative. In this paper we demonstrate the optimization path of a newly developed peptide synthesizer in the context of coupling reagents, reaction time and reagent equivalents applying for a synthesis of a model peptide. We compare the results by analytical characteristics (purity of raw material, crude yield, yield) and calculated overall cost of the syntheses of one mg of crude peptide using a specified set of reaction conditions. |
| first_indexed | 2024-04-09T20:07:21Z |
| format | Article |
| id | doaj.art-2e9a9c1ea30747f2ae680cf7ccb4efeb |
| institution | Directory Open Access Journal |
| issn | 2472-6303 |
| language | English |
| last_indexed | 2024-04-09T20:07:21Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | SLAS Technology |
| spelling | doaj.art-2e9a9c1ea30747f2ae680cf7ccb4efeb2023-04-01T08:51:02ZengElsevierSLAS Technology2472-63032023-04-012828997Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesisKrisztina Kiss0Soma Ránky1Zsuzsanna Gyulai2László Molnár3Tavanta Therapeutics Hungary Zrt., H-1138 Budapest, Hungary; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics (BME), H-1111 Budapest, HungaryTavanta Therapeutics Hungary Zrt., H-1138 Budapest, HungaryTavanta Therapeutics Hungary Zrt., H-1138 Budapest, HungaryTavanta Therapeutics Hungary Zrt., H-1138 Budapest, Hungary; Corresponding author at: H-1138 Budapest, Madarász Viktor u. 47-49, Hungary.The development of peptide-based pharmaceutics is a hot topic in the pharmaceutical industry and in basic research. However, from the research and development perspective there is an unmet need for new, alternative, solid-phase peptide synthesizers that are highly efficient, automated, robust, able to synthetize peptides in parallel, inexpensive (to obtain and operate), have potential to be scaled up, and even comply with the principles of green chemistry. Moreover, a peptide synthesizer of this type could also fill the gap in university research, and therefore speed the advancement of peptide-based pharmaceutical options. This paper presents a Tecan add-on peptide synthesizer (TaPSy), which has operational flexibility (coupling time: 15–30 min), can handle all manual synthesis methods, and is economical (solvent use: 34.5 mL/cycle, while handling 0.49 mmol scale/reactor, even with ≤3 equivalents of activated amino acid derivatives). Moreover, it can carry out parallel synthesis of up to 12 different peptides (0.49 mmol scale in each). TaPSy uses no heating or high pressure, while it is still resistant to external influences (operating conditions: atmospheric pressure, room temperature 20–40 ˚C, including high [>70%] relative humidity). The system's solvent can also be switched from DMF to a green and biorenewable solvent, γ-valerolactone (GVL), without further adjustment. The designed TaPSy system can produce peptides with high purity (>70%), even with the green GVL solvent alternative. In this paper we demonstrate the optimization path of a newly developed peptide synthesizer in the context of coupling reagents, reaction time and reagent equivalents applying for a synthesis of a model peptide. We compare the results by analytical characteristics (purity of raw material, crude yield, yield) and calculated overall cost of the syntheses of one mg of crude peptide using a specified set of reaction conditions.http://www.sciencedirect.com/science/article/pii/S2472630323000031Solid-phase peptide synthesisAutomatedHigh-throughputRobustParallel synthesisTecan add-on peptide synthesizer |
| spellingShingle | Krisztina Kiss Soma Ránky Zsuzsanna Gyulai László Molnár Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis SLAS Technology Solid-phase peptide synthesis Automated High-throughput Robust Parallel synthesis Tecan add-on peptide synthesizer |
| title | Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis |
| title_full | Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis |
| title_fullStr | Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis |
| title_full_unstemmed | Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis |
| title_short | Development of a novel, automated, robotic system for rapid, high-throughput, parallel, solid-phase peptide synthesis |
| title_sort | development of a novel automated robotic system for rapid high throughput parallel solid phase peptide synthesis |
| topic | Solid-phase peptide synthesis Automated High-throughput Robust Parallel synthesis Tecan add-on peptide synthesizer |
| url | http://www.sciencedirect.com/science/article/pii/S2472630323000031 |
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