Delivery of polypeptides in multi-kilogram quantities within commercially competitive timelines is extremely challenging, especially when coupled with a desire to minimize environmental and economic impact. This case study explores how CPC Scientific’s advanced process improvements and efficiencies within solid-phase peptide synthesis (SPPS) have enabled multi-kilogram delivery of a pharmaceutically-relevant decapeptide within a challenging timescale, driving sustainable and cost-saving production for the client.
Our team has developed an innovative DMF recycling strategy that substantially reduces solvent consumption during solid-phase peptide synthesis. Minimizing use of DMF, a major environmental and cost contributor in peptide manufacturing, has improved process sustainability and cost efficiency. This method neatly demonstrates how targeted green chemistry practices can be successfully integrated into large-scale SPPS, supporting more environmentally responsible and economically viable peptide production.
The peptides found naturally in the human skin play essential roles in specific biological activities as signaling molecules of different physiological processes (i.e., homeostasis, defense, immunity). Due to their great biological activity, peptides are considered promising compounds with potential applications for certain cosmetic products. CPC Scientific possesses the manufacturing capabilities to assist with your cosmetic peptide projects, ranging from early discovery (mg quantities) to commercialization (100 kgs). Our pre-qualified workspace and adaptable approach enable us to expedite process development and commence production earlier than many other manufacturers.
Gain insights from Joseph Denby's rapid-fire Q&A spotlight at NextGen Biomed, where he explores the landscape of peptide and oligo APIs, as well as the role of green chemistry in manufacturing.
The synthesis of the linear RP-182 analog, bicyclo[6.1.0]non-4-yn-9-ylmethyloxycarbonyl-PEG2-Lys-Phe-Arg-Lys-Ala-Phe-Lys-Arg-Phe-Phe-Lys(azido-PEG)-NH2, was achieved using standard solid-phase peptide synthesis (SPPS) protocols. After cleaving the linear peptide from the resin, macrocyclization was performed in the liquid phase through a strain-promoted click reaction. BCN introduces extra ring strain due to its fused cyclopropane structure. The combined effect of ring strain, the selection of BCN, and copper catalysis significantly increases the macrocyclization efficiency of longer peptides like RP-182.
Singh, S.S., Calvo, R., Kumari, A., Sable, R.V., Fang, Y., Tao, D., Hu, X., Castle, S.G., Nahar, S., Li, D. and Major, E. Molecular Cancer Therapeutics (2024).
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[..] assembling the peptide on the Rink Amide resin and attaching the PEG azide moiety to the N-terminal Lys, the Dde group was removed as previously shown and coupled to the Fmoc-PEG2-acid. Removal of the Fmoc followed by simultaneously click/coupling to bicyclo[6.1.0]non-4-yn-9-ylmethyl (2,5-dioxopyrrolidin-1-yl) carbonate gave 1c which was deprotected and cleaved from the resin to give 1c.
This poster introduces two methodology case studies involving minimal side-chain protection strategies for solid-phase peptide synthesis (SPPS). SPPS approaches require protecting the sidechains of specific amino acids to avoid undesired reactivity during synthesis. Installing and removing these protection groups results in a lower atom economy in the production process and excess chemical waste.
Solid-phase peptide synthesis (SPPS) approaches require that the side chains of certain amino acids be protected from undesired reactivity during synthesis. The installation and removal of these protection groups results in a lower atom economy in the production process. Removal of the protection groups often requires large volumes of trifluoroacetic acid (TFA) or other strong acids which can result in lower yields and pose a significant risk to the environment.
