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bioRxiv · 10.1101/2020.03.05.978098

An Artificial Cofactor catalyzing the Baylis-Hillman Reaction using Designed Streptavidin as Protein Host

Lechner, H.·Emann, V. R.·Breuning, M.·Hoecker, B.
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Abstract

An artificial cofactor based on an organocatalyst embedded in a protein was used to conduct the Baylis-Hillman reaction in a buffered system. As protein host we chose streptavidin, since it can be easily crystallized and thereby supports the design process. The protein host around the cofactor was rationally designed based on high-resolution crystal structures obtained after each variation of the amino acid sequence. Additionally, DFT-calculated intermediates and transition states were used to rationalize activity. Finally, repeated cycles of structure determination and redesign led to a system with 24 to 35-fold increased activity over the bare cofactor and to the most active proteinogenic catalyst for the Baylis-Hillman reaction known today.

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Lechner, H., Emann, V. R., Breuning, M., Hoecker, B.. 2020-03-05. An Artificial Cofactor catalyzing the Baylis-Hillman Reaction using Designed Streptavidin as Protein Host. https://doi.org/10.1101/2020.03.05.978098

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