Enantioselectivity biotin-avidin technology

Chem. Soc., 126, 14411-14418 Skander, M., Malan, C., Ivanova, A. and Ward, TR. (2005) Chemical optimization of artificial metaUoenzymes based on the biotin-avidin technology (S)-selective and solvent-tolerant hydrogenation catalysts via the introduction of chiral amino acid spacers. Chem. Commun., 4815-4817 Ward, TR. (2005) Artificial metallo-enzymes for enantioselective catalysis based on the noncovalent incorporation of organometallic moieties in a host protein. Chem.-Eur. J., 11, 3798-3804 Letondor, C. and Ward, TR. (2006) Artificial metaUoenzymes for enantioselective catalysis Recent advances. Chem. Bio. Chem., 7, 1845-1852. 

Letondor, C., Humbert, N. and Ward, TR. (2005) Artificial metaUoenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation. Proc. Natl. Acad. Sci. U.S.A., 102, 4683-4687 Letondor, C., Pordea, A., Humbert, N., Ivanova, A., Mazurek, S., Novic, M. and Ward, TR. (2006) Artificial transfer hydrogenases based on the biotin-(strept)avidin technology Fine tuning the selectivity by saturation mutagenesis of the host protein. J. Am. Chem. Soc., 128, 8320-8328. 

Artificial Metalloenzymes for Enantioselective Catalysis Based on the Biotin-Avidin Technology... 

Key words Allylic alkylation, Artificial metalloenzyme, Biotin-avidin technology, Chemogenetic optimization, Designed evolution, Enantioselective catalysis. Hybrid catalyst. Hydrogenation, Streptavidin, Transfer hydrogenation. 

We reasoned that one could mimic Nature by incorporating cofactors and metal ions to broaden the scope of accessible reactions catalyzed by protein scaffolds. Different approaches for the generation of artificial metalloenzymes have recently been reviewed [2-16]. Herein, we present the developments in the field of artificial metalloenzymes for enantioselective catalysis based on the biotin-avidin technology. The discussion includes a short introduction on the biotin-avidin technology followed by several examples of chemogenetic optimization of the performance of artificial metalloenzymes based on this technology. 

Fig. 2 Biotin-avidin technology Artificial metalloenzymes [M(L )(biotin-ligand)]c(strept)avidin for enantioselective catalysis are based on the anchoring of a catalyticaUy active metal fragment within a host protein via a hgand, a spacer, and biotin. Chemical optimization can be achieved either by varying the spacer or the metal chelate moiety ML ). Saturation mutagenesis at a position close to the metal moiety ( ) can be used for genetic optimization...

Inspired by the visionary paper of Whitesides, we adapted and extended the concept of artificial metalloenzymes (or hybrid catalysts) based on the biotin-avidin technology to enantioselective hydrogenation, transfer hydrogenation, and aUyhc alkylation reactions, which are summarized herein. 

In summary, relying on a chemogenetic optimization procedure, we have produced artificial hydrogenases based on the biotin-avidin technology for the enantioselective reduction of N-protected dehydroaminoacids [up to 96% ee (R) and 95% ee (5)] [36, 39]. Next, we outhne our recent findings in artificial aUylic... 

Ward TR (2011) Artificial metalloenzymes based on the biotin-avidin technology enantioselective catalysis and beyond. Acc Chem Res 44 47-57... 

As summarized here, artificial metalloenzymes based on the biotin-avidin technology have developed into a versatile approach to enantioselective catalysis. In many cases, selectivities exceeding 92% ee could be obtained, relying on a chemogenetic optimization strategy. Such hybrid catalysts display features which are reminiscent of both homogeneous and enzymatic catalysis. 

C. Letondor, N. Humbert, T. R. Ward, Artificial metalloenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation, Proc. Natl. Acad. Sci. USA, 2005, 102, 4683-4687. 

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