Abstract

Continuous Peptide Formation in the Aqueous Phase

Katherine Jolley, Postdoctoral Research Fellow, University of Leeds

[FROM SPEAKER] Solid phase peptide synthesis[1] is conventionally the preferred method for peptide formation. Despite significant developments within the field the approach still has some drawbacks including use of atom inefficient protecting groups and coupling agents, undesirable solvents and low product yields. As an alternative we present the development of a continuous process for protecting group free, aqueous solution phase peptide formation. Previous literature describes the formation of peptides by reaction of amino acid derived N-carboxyanhydrides with amino acids under basic conditions.[2] Rapid mixing, pH and temperature control were shown to be key reaction parameters. We have developed a continuous stirred tank reactor allowing continuous addition of solid reagents, high shear mixing and efficient pH and temperature control for the continuous formation of peptides. Studies have also been carried out to gain further understanding of the reaction profile and the effect of key parameters on product formation. [1] Merrifield, R. B., Angew. Chem. Int. Ed., 1985, 25(10), 799-892. [2] Hirschmann, R. Strachan, R. G.; Schwam, H.; Schoenewaldt, E. F.; Joshua, H.; Barkemeyer, B.; Veber, D. F.; Paleveda Jr., W. J.; Jacob, T. A.; Beesley, T. E. and Denkewalter, R. G., J. Am. Chem. Soc., 1967, 89, 3415-3425.