Development of an Interactive Green Solvent Selection Guide for Solid-Phase Peptide Synthesis (SPPS)
Jenna M. Mowat,a* Andrew Kennedy,bLukasz Frankiewicz,b and Craig Jamiesonaa
aDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL. bGyros Protein Technologies Inc., 4675 South Coach Drive, Tucson, Arizona, 85714, USA
The use of peptides as therapeutics has gained traction over the years and with the current adopted protocol to synthesize these biomolecules - requiring large volumes of hazardous solvents such as DMF, NMP and DCM, in addition to large excess of coupling reagents being essential, there is a great need to develop a more sustainable process that is closely aligned with the twelve principles of ‘Green Chemistry’. The use of green solvents in solid-phase peptide synthesis has been explored with some DMF replacements being identified, but these alternative solvents haven’t been readily adopted into practice. Equipped with literature in hand, using the physical properties of selected solvents, including previously identified greener alternatives - as well as the standard SPPS solvents, the authors of this poster have developed an interactive solvent guide using DataWarrior software for solid-phase peptide synthesis. Swelling capabilities, amino acid and coupling agent solubility, and Fmoc deprotection compatibility were tested for an array of green solvents and solvent mixtures. This study allowed for the identification of cyclopentanone as a suitable replacement for DMF, and facilitated the successful assembly of leu-enkephalin on both polystyrene and ChemMatrix based resins.