A Sustainable Solid-Phase Peptide Synthesis Approach
This month, we want to draw your attention to the topic of sustainability in peptide synthesis. The article “In Situ Fmoc Removal – A Sustainable Solid-Phase Peptide Synthesis Approach” (Kumar et al., 2022), while a few years old, remains highly relevant. The authors pave the way for the concept of peptide sustainability and green chemistry by introducing a clever method to reduce solvent waste.
Until green solvents for solid-phase peptide synthesis (SPPS) become widely accepted in the industry, it's crucial to work towards minimizing the environmental impact of existing SPPS practices. This article addresses one of the largest sources of solvent consumption in solid peptide synthesis: the solvents used for resin washes.
The authors propose a method that combines acylation and Fmoc deprotection by directly adding neat piperidine to the spent solution containing residual amino acids and oxyma. This approach effectively telescopes the acylation reaction into the deprotection step, which they refer to as in situ Fmoc deprotection. This practical solution is exactly what the industry needs to tackle the short-term issues related to process mass intensity (PMI) in SPPS. The authors demonstrate that this method does not compromise the final product; they achieve peptide materials of equal purity compared to standard SPPS.
Another reason we selected this article is that its corresponding author and inspiration is Professor Fernando Albericio.
Professor Albericio has been a prominent figure in solid-phase peptide chemistry for the past 50 years, developing numerous reagents that are essential for peptide chemists in their daily syntheses. Recently, he has made significant contributions to green chemistry, focusing on environmentally friendly methods for peptide synthesis. Given the rising interest in peptides as potential drugs, such as GLP-1, his work is increasingly important. His dedication to replacing hazardous solvents like DMF, DCM, and NMP with safer, less toxic alternatives is consistently evident in his numerous recent publications on this topic.
Professor Albericio was recently honored with the Meienhofer Award for excellence in peptide sciences at the Boulder Peptide Symposium in Boulder, CO. His lecture was well received by attendees. His research emphasizes scaling up peptide synthesis for pharmaceutical applications, enabling the production of large quantities of peptides with minimal environmental impact. He has pioneered the use of greener solvents, such as water, achieving high yields and purity, and has conducted detailed studies on the properties of green solvents in SPPS. Additionally, he is exploring new protecting groups that are easily removed and generate less waste.
His career continues to inspire many students, and his commitment to green chemistry is a testament to his dedication to the field of peptide chemistry.
Kumar, A., Sharma, A., de la Torre, B.G., and Albericio, F. (2022). In situ Fmoc removal – a sustainable solid-phase peptide synthesis approach. Green Chemistry, 24, 4887-4896. Link to publication
Professor Pravin Kaumaya, Ph.D.
Indiana University School of Medicine
Member, BPF Scientific Advisory Board
Matteo Villain, PharmD.
Member, BPF Scientific Advisory Board
linkedin.com/in/matteo-villain
Read previous editions of the BPF Journal Club series: https://www.boulderpeptide.org/journal-club