Solid-phase synthesis is the most common strategy to produce peptides. For over a decade it has been assumed that fast mixing destroys the solid support beads. Hence, SPPS employs only gentle mixing methods to preserve the integrity of the beads. These common SPPS mixing methods suffer from poor heat transfer and slow diffusion rates. Instead of trying to improve the mixing efficiency, the above disadvantages were tackled by employing huge excess of highly reactive reagents, by increasing the temperature, by elongating the reaction duration, or by combining all three. It has been recently shown that fast SPPS can be achieved by performing the reactions in flow reactors at high temperatures, albeit, while still using a large excess of reagents.<br/>We showed for the first time that high-shear mixing can be employed for SPPS without harming the beads. We relied on Fick principles and showed that highly efficient SPPS can be achieved simply by exploiting the fast diffusion and heat transfer rates gained by applying over 1000 RPM overhead stirring. High-shear mixing eabled reaching fast and highly efficient SPPS without using a large excess of reagents.<br/>All indications show that fast stirring improves dramatically the efficiency of SPPS. The strategy has practical and economic advantages that are rooted in fundamental thermodynamic and kinetic principles. The use of fast stirring SPPS will lead to a new way for the preparation of peptides and bioactive molecule libraries in the future.

Stirring solid-phase peptide synthesis to a new level of efficiency

ACS Spring Meeting 2021

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