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Diffusional Limitations during Solid Phase Peptide Synthesis

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Peptide therapeutics have immense potential for a variety of molecular targets. Their low toxicity makes them very desirable for oncology and other areas including personalized medicine. However, large-scale peptide manufacturing is expensive with large waste e-factors. Long coupling, deprotection, washout times, and potential diffusional limitations hinder solid phase peptide synthesis (SPPS), generating tremendous solvent and reagent waste. This report aims to identify the cause of these problems, determine how to decrease these inefficiencies, and minimize the time needed per coupling. Residence time distribution experiments were run to understand the time it takes for an amino acid to flow through the reactor as well as the dispersion present during synthesis. A zero-length chromatography (ZLC) column was used to characterize diffusion limitations in which the uptake and release of a tracer amino acid through resin was measured and then analyzed. Ultimately, it was found that hydrodynamic oscillations lower the residence time and reducing headspace lowers the dispersion in the reactor. The system was found to be diffusion limited 4-5 minutes after initial release of the tracer amino acid. By reducing the headspace, retaining the oscillation, and controlling the flow rate after the initial washout period, SPPS processes are optimized with less waste and less cost, making the process more sustainable.

  • This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.
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Identifier
  • 64616
  • E-project-042722-174256
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Year
  • 2022
Sponsor
UN Sustainable Development Goals
Date created
  • 2022-04-27
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Permanent link to this page: https://digital.wpi.edu/show/4b29b937h