Towards green, scalable peptide synthesis: leveraging DEG-crosslinked polystyrene resins to overcome hydrophobicity challenges

Othman Al Musaimi; Joshua Tomkins; Sarah M. Barry; Alessandra Basso; Xiaokang Kou; Cheng Zhang; Simona Serban

doi:10.1039/d4ra07484j

Towards green, scalable peptide synthesis: leveraging DEG-crosslinked polystyrene resins to overcome hydrophobicity challenges

Othman Al Musaimi^*, Joshua Tomkins, Sarah M. Barry, Alessandra Basso, Xiaokang Kou, Cheng Zhang, Simona Serban^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Diethylene glycol dimethacrylate (DEG)-crosslinked polystyrene (PS) resin offers a promising alternative to traditional divinyl benzene (DVB)-PS resin for solid-phase peptide synthesis (SPPS), particularly for challenging sequences with hydrophobic or bulky amino acids. DEG-PS resin's reduced hydrophobicity and enhanced flexibility improve synthesis efficiency, yielding peptides up to 28 residues with higher purities and yields compared to DVB-PS. In various syntheses, DEG-PS outperformed DVB-PS resin, with higher purities and yields for challenging peptides such as ABC analogue (73.2%, 58.3% vs. 72.5%, 46.3%) and Thymosin (58.4%, 48.6% vs. 54.0%, 39.2%). In addition, DEG-PS resin effectively suppressed common side reactions, such as dipeptide formation, typically encountered with Wang PS-based resins. Incorporating green chemistry principles, DEG-PS enabled the synthesis of complex peptides with satisfactory results using environmentally friendly solvents and reagents. Three challenging peptides; β (34-42), Jung and Redemann (JR), and ABRF 1992 - were synthesized on DEG-PS resin, achieving purities of 41.4%, 41.0%, and 68.0%, and yields of 50.5%, 52.6%, and 56.2%, respectively. These findings highlight DEG-PS resin's advantages for classical, green, and automated SPPS, offering superior performance and scalability for industrial applications.

Original language	English
Pages (from-to)	40255-40266
Number of pages	12
Journal	RSC Advances
Volume	14
Issue number	54
DOIs	https://doi.org/10.1039/d4ra07484j
Publication status	Published - 23 Dec 2024

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title = "Towards green, scalable peptide synthesis: leveraging DEG-crosslinked polystyrene resins to overcome hydrophobicity challenges",

abstract = "Diethylene glycol dimethacrylate (DEG)-crosslinked polystyrene (PS) resin offers a promising alternative to traditional divinyl benzene (DVB)-PS resin for solid-phase peptide synthesis (SPPS), particularly for challenging sequences with hydrophobic or bulky amino acids. DEG-PS resin's reduced hydrophobicity and enhanced flexibility improve synthesis efficiency, yielding peptides up to 28 residues with higher purities and yields compared to DVB-PS. In various syntheses, DEG-PS outperformed DVB-PS resin, with higher purities and yields for challenging peptides such as ABC analogue (73.2%, 58.3% vs. 72.5%, 46.3%) and Thymosin (58.4%, 48.6% vs. 54.0%, 39.2%). In addition, DEG-PS resin effectively suppressed common side reactions, such as dipeptide formation, typically encountered with Wang PS-based resins. Incorporating green chemistry principles, DEG-PS enabled the synthesis of complex peptides with satisfactory results using environmentally friendly solvents and reagents. Three challenging peptides; β (34-42), Jung and Redemann (JR), and ABRF 1992 - were synthesized on DEG-PS resin, achieving purities of 41.4%, 41.0%, and 68.0%, and yields of 50.5%, 52.6%, and 56.2%, respectively. These findings highlight DEG-PS resin's advantages for classical, green, and automated SPPS, offering superior performance and scalability for industrial applications.",

author = "{Al Musaimi}, Othman and Joshua Tomkins and Barry, {Sarah M.} and Alessandra Basso and Xiaokang Kou and Cheng Zhang and Simona Serban",

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AU - Tomkins, Joshua

AU - Barry, Sarah M.

AU - Basso, Alessandra

AU - Kou, Xiaokang

AU - Zhang, Cheng

AU - Serban, Simona

PY - 2024/12/23

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AB - Diethylene glycol dimethacrylate (DEG)-crosslinked polystyrene (PS) resin offers a promising alternative to traditional divinyl benzene (DVB)-PS resin for solid-phase peptide synthesis (SPPS), particularly for challenging sequences with hydrophobic or bulky amino acids. DEG-PS resin's reduced hydrophobicity and enhanced flexibility improve synthesis efficiency, yielding peptides up to 28 residues with higher purities and yields compared to DVB-PS. In various syntheses, DEG-PS outperformed DVB-PS resin, with higher purities and yields for challenging peptides such as ABC analogue (73.2%, 58.3% vs. 72.5%, 46.3%) and Thymosin (58.4%, 48.6% vs. 54.0%, 39.2%). In addition, DEG-PS resin effectively suppressed common side reactions, such as dipeptide formation, typically encountered with Wang PS-based resins. Incorporating green chemistry principles, DEG-PS enabled the synthesis of complex peptides with satisfactory results using environmentally friendly solvents and reagents. Three challenging peptides; β (34-42), Jung and Redemann (JR), and ABRF 1992 - were synthesized on DEG-PS resin, achieving purities of 41.4%, 41.0%, and 68.0%, and yields of 50.5%, 52.6%, and 56.2%, respectively. These findings highlight DEG-PS resin's advantages for classical, green, and automated SPPS, offering superior performance and scalability for industrial applications.

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Towards green, scalable peptide synthesis: leveraging DEG-crosslinked polystyrene resins to overcome hydrophobicity challenges

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