Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides
In recent years, peptides have gained more success as therapeutic compounds. Nowadays, the preferred method to obtain peptides is solid-phase peptide synthesis (SPPS), which does not respect the principles of green chemistry due to the large number of toxic reagents and solvents used. The aim of thi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/6/1773 |
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| author | Giovanni Vivenzio Maria Carmina Scala Pasquale Marino Michele Manfra Pietro Campiglia Marina Sala |
| author_facet | Giovanni Vivenzio Maria Carmina Scala Pasquale Marino Michele Manfra Pietro Campiglia Marina Sala |
| author_sort | Giovanni Vivenzio |
| collection | DOAJ |
| description | In recent years, peptides have gained more success as therapeutic compounds. Nowadays, the preferred method to obtain peptides is solid-phase peptide synthesis (SPPS), which does not respect the principles of green chemistry due to the large number of toxic reagents and solvents used. The aim of this work was to research and study an environmentally sustainable solvent able to replace dimethylformamide (DMF) in fluorenyl methoxycarbonyl (Fmoc) solid-phase peptide synthesis. Herein, we report the use of dipropyleneglycol dimethylether (DMM), a well-known green solvent with low human toxicity following oral, inhalant, and dermal exposure and that is easily biodegradable. Some tests were needed to evaluate its applicability to all the steps of SPPS, such as amino acid solubility, resin swelling, deprotection kinetics, and coupling tests. Once the best green protocol was established, it was applied to the synthesis of different length peptides to study some of the fundamental parameters of green chemistry, such as PMI (process mass intensity) and the recycling of solvent. It was revealed that DMM is a valuable alternative to DMF in all steps of solid-phase peptide synthesis. |
| first_indexed | 2024-03-11T02:01:43Z |
| format | Article |
| id | doaj.art-2b314cebd5ed4333999c3167cc89f7bb |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T02:01:43Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2b314cebd5ed4333999c3167cc89f7bb2023-11-18T12:06:20ZengMDPI AGPharmaceutics1999-49232023-06-01156177310.3390/pharmaceutics15061773Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic PeptidesGiovanni Vivenzio0Maria Carmina Scala1Pasquale Marino2Michele Manfra3Pietro Campiglia4Marina Sala5Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, 84084 Salerno, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, 84084 Salerno, ItalyDepartment of Sciences, University of Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Sciences, University of Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, 84084 Salerno, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano, 84084 Salerno, ItalyIn recent years, peptides have gained more success as therapeutic compounds. Nowadays, the preferred method to obtain peptides is solid-phase peptide synthesis (SPPS), which does not respect the principles of green chemistry due to the large number of toxic reagents and solvents used. The aim of this work was to research and study an environmentally sustainable solvent able to replace dimethylformamide (DMF) in fluorenyl methoxycarbonyl (Fmoc) solid-phase peptide synthesis. Herein, we report the use of dipropyleneglycol dimethylether (DMM), a well-known green solvent with low human toxicity following oral, inhalant, and dermal exposure and that is easily biodegradable. Some tests were needed to evaluate its applicability to all the steps of SPPS, such as amino acid solubility, resin swelling, deprotection kinetics, and coupling tests. Once the best green protocol was established, it was applied to the synthesis of different length peptides to study some of the fundamental parameters of green chemistry, such as PMI (process mass intensity) and the recycling of solvent. It was revealed that DMM is a valuable alternative to DMF in all steps of solid-phase peptide synthesis.https://www.mdpi.com/1999-4923/15/6/1773green chemistrysolid-phase peptide synthesispeptidesdipropyleneglycol dimethyletherrecycling |
| spellingShingle | Giovanni Vivenzio Maria Carmina Scala Pasquale Marino Michele Manfra Pietro Campiglia Marina Sala Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides Pharmaceutics green chemistry solid-phase peptide synthesis peptides dipropyleneglycol dimethylether recycling |
| title | Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides |
| title_full | Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides |
| title_fullStr | Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides |
| title_full_unstemmed | Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides |
| title_short | Dipropyleneglycol Dimethylether, New Green Solvent for Solid-Phase Peptide Synthesis: Further Challenges to Improve Sustainability in the Development of Therapeutic Peptides |
| title_sort | dipropyleneglycol dimethylether new green solvent for solid phase peptide synthesis further challenges to improve sustainability in the development of therapeutic peptides |
| topic | green chemistry solid-phase peptide synthesis peptides dipropyleneglycol dimethylether recycling |
| url | https://www.mdpi.com/1999-4923/15/6/1773 |
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