An affordable and low-waste protocol for rapid and robust solid-phase peptide synthesis at elevated temperatures

Area of Science:

• Organic Chemistry
• Biochemistry
• Analytical Chemistry

Background:

• Automated solid-phase peptide synthesis (SPPS) is crucial for high-purity peptide production.
• Current automated SPPS methods often involve expensive equipment and generate substantial chemical waste.
• There is a need for accessible, cost-effective, and sustainable peptide synthesis protocols.

Purpose of the Study:

• To develop a robust and accessible solid-phase peptide synthesis (SPPS) protocol.
• To achieve rapid peptide synthesis using standard laboratory equipment, mimicking microwave-assisted thermal acceleration.
• To evaluate the cost-effectiveness, waste reduction, and stereochemical integrity of the developed SPPS method.

Main Methods:

• Development of a novel SPPS protocol utilizing standard laboratory equipment for thermal acceleration.
• Synthesis of diverse linear and cyclic peptides at the 10-100 mg scale.
• Multi-modal analytical assessment including HPLC, NMR, and ion mobility mass spectrometry to investigate epimerization risks.

Main Results:

• The developed SPPS protocol enables rapid peptide assembly with reaction times reduced to minutes.
• Significant reduction in chemical waste compared to conventional automated SPPS methods.
• Satisfactory crude yields and purities were obtained, with high stereochemical fidelity maintained.
• Synthesized peptides retained native biochemical function, confirmed by analysis of two active sequences.

Conclusions:

• The presented SPPS protocol offers a highly accessible and cost-effective alternative to expensive automated systems.
• This method successfully reduces reaction times and chemical waste while preserving peptide quality and stereochemical integrity.
• The protocol is suitable for producing a diverse range of peptides, including biochemically active sequences, with high fidelity.