Poster Presentation 7th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2019

Fast Solid Phase Peptide Synthesis method development for the synthesis of sterically hindered peptides (#127)

Cyf Ramos-Colon 1 , Daniel Martinez 1 , Andrew Kennedy 1 , James Cain 1
  1. Gyros Protein Technologies, Tucson, AZ, United States

With the advancement of peptides into the clinic, the complexity of peptide sequences has continued to increase. With more complex sequences, synthesis difficulties arise, for example, sterically hindered coupling reactions and increased hydrophobicity, among others. Parallel synthesis optimization with induction heating was performed on the solid phase peptide synthesis (SPPS) of several sterically hindered peptides, like Aib-ACP (H-VQ-Aib-Aib-IDYING-NH2) and N-methylated peptides. Methods for SPPS of linear peptides have seen improvements with increased temperature protocols (>50 °C), resulting in shorter coupling cycles and higher crude purity [1-2]. In the synthesis of Aib-ACP an increase in peptide purity of 30% was observed just by increasing the temperature during synthesis. Here we describe the use of different coupling reagents, different temperatures and reaction times in parallel searching for improvements in crude peptide purity using fast reaction times.

  1. Bacsa, B.; Horváti, K.; Bõsze, S.; Andreae, F.; Kappe, C. O. J. Org. Chem. 2008, 73 (19), 7532–7542.
  2. Behrendt, R.; White, P.; Offer, J. J. Pept. Sci. 2016, 22 (1), 4–27.