Handling synthetic peptides, particularly those containing hydrophobic sequences or cysteine residues, can present challenges during the synthesis and purification processes due to the use of Dimethyl Sulfoxide (DMSO) and thiol scavengers. These components are essential in peptide synthesis for solubilizing peptides and protecting the thiol groups of cysteine from oxidation but can result in strong and offensive odors and, sometimes, difficulty in removing scavengers from the final product.
An additional round of purification columns can often mitigate the offensive odors associated with large quantities of DMS and thiol scavengers. While it might be challenging to remove sulfur-containing scavengers used in the deprotection steps, these do not usually affect the purity of the final peptide product.
Incorporating green chemistry principles into peptide synthesis not only addresses the environmental impact but also enhances the sustainability of the synthesis process. Innovations in peptide synthesis, such as the introduction of unnatural amino acids, cyclization, and conjugation techniques, have improved the pharmacokinetic properties of peptides, making them more viable as pharmaceutical agents. Despite these advancements, the purification stage remains critical for removing odorous by-products and ensuring the peptide's therapeutic efficacy.
The choice of cleavage cocktail and scavengers is crucial for peptides containing cysteine. Cysteine's sulfhydryl side chain is highly reactive, and without proper protection, it can lead to unwanted side reactions or oxidation. Ethanedithiol (EDT) is often used as a reducing agent in the cleavage cocktail to maintain cysteine residues in a reduced state, preventing their oxidation and ensuring the integrity of the peptide.
Addressing these challenges requires a careful balance between efficient synthesis techniques and sustainable, environmentally friendly purification processes. By optimizing both synthesis and purification, it is possible to produce high-quality peptides with minimal environmental impact, thus enhancing the feasibility of peptide-based therapeutics.
For further detailed insights into peptide synthesis and purification, exploring resources on sustainable peptide chemistry and the role of scavengers in cleavage cocktails can provide valuable information.