Poster Presentation 11th Australian Peptide Conference 2015

Optimizing Solid Phase Peptide Synthesis at Elevated Temperature (#113)

Jonathan M Collins 1 , Sandeep K Singh 1 , Keith A Porter 1
  1. CEM Corporation, Matthews, NC, United States

The development of HE-SPPS has improved the efficiency of SPPS with its high purity characteristics, rapid 4 min cycle times, and significant waste reduction [1]. More recently, an improved carbodiimide based coupling method has been developed and applied at a 0.005 – 150 mmol scale range toward a difficult peptide using a larger scale microwave synthesizer. Improvements from this new coupling method include overall coupling efficiency, phosphopeptide synthesis, and stability of the hyper-acid sensitive Trityl linker at 90°C [2]. An additional benefit was realized from the development of a novel Trityl based linker which allows for on-demand loading of the first amino acid without activation, while maintaining a relatively high stability toward hydrolysis. Finally, a new process is presented which allows for further improvements toward the overall SPPS process based on insights to the deprotection and washing steps. This new process has reduced the overall cycle time and chemical waste further.

  1. Collins, J., Porter, K., Singh, S., Vanier, G. Org Lett. 2014, 16, 940-943.
  2. Manuscript in Preparation; Patent Pending