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Updated: Apr 10, 2026

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Solid-phase Submonomer Synthesis of Peptoid Polymers and their Self-Assembly into Highly-Ordered Nanosheets
Published on: November 2, 2011
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Nanoassembly-enabled aqueous solid-phase peptide synthesis (ASPPS): a practical DMF-free approach based on the Fmoc
Keiko Hojo1,2, Ayumi Nonaka1, Yuki Manabe1
1Faculty of Pharmaceutical Sciences, Kobe Gakuin University Kobe 650-8586 Japan hojo@pharm.kobegakuin.ac.jp kunisima@pharm.kobegakuin.ac.jp.
RSC Advances
|April 9, 2026
Summary
Researchers developed a green peptide synthesis method using water instead of hazardous solvents. This novel approach utilizes nanoassemblies for efficient peptide bond formation, offering a sustainable alternative for manufacturing peptides.
Area of Science:
- Green Chemistry
- Biotechnology
- Organic Synthesis
Background:
- Conventional N,N-dimethylformamide (DMF)-based solid-phase peptide synthesis (SPPS) relies on hazardous organic solvents, posing environmental concerns.
- There is a growing demand for sustainable and eco-friendly methods in peptide manufacturing.
Purpose of the Study:
- To develop a practical and greener alternative to conventional DMF-based SPPS.
- To introduce a water-based SPPS protocol that eliminates hazardous organic solvents.
Main Methods:
- Leveraging nanoassemblies formed from Fmoc-protected amino acids, coupling reagents, and bases in an aqueous medium.
- Utilizing the reactive interfacial microenvironments created by nanoassemblies to enhance local concentration and promote peptide bond formation.
- Employing microwave-assisted coupling for scalability and semi-automation.
Main Results:
- Successful synthesis of various peptides, including β-endorphin (31 residues), using the water-based nanoassembly method.
- Achieved yields and purities comparable to those obtained with conventional DMF-based SPPS.
- Demonstrated the compatibility of the nanoassembly approach with existing SPPS platforms and microwave-assisted coupling.
Conclusions:
- The developed method provides a simple, eco-friendly, and practical platform for peptide synthesis aligned with green chemistry principles.
- This reaction-field-based strategy using nanoassemblies offers a sustainable alternative for peptide manufacturing.
- The approach eliminates the need for hazardous organic solvents, reducing environmental impact.

