Enantioselectivity streptavidin

Figure 3.7 The biotin-streptavidin system for enantioselective hydrogenation.

Some researchers have begun to explore the possibihty of combining transition metal catalysts with a protein to generate novel synthetic chemzymes . The transition metal can potentially provide access to novel reaction chemistry with the protein providing the asymmetric environment required for stereoselective transformations. In a recent example from Reetz s group, directed evolution techniques were used to improve the enantioselectivity of a biotinylated metal catalyst linked to streptavidin (Scheme 2.19). The Asn49Val mutant of streptavidin was shown to catalyze the enantioselective hydrogenation of a-acetamidoacrylic acid ester 46 with moderate enantiomeric excess [21]. 

Y Tanaka, S Terabe. Studies of enantioselectivities of avidin, avidin-biotin complex and streptavidin by affinity capillary electrophoresis. Chromatographia 49 489-495, 1999. 

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

Proteins as Host for Enantioselective Catalysis Artificial Metalloenzymes Based on the Biotin-Streptavidin Technology... 

Enantioselective Sulfoxidation Based on Vanadyl-loaded Streptavidin... 

A. Pordea, M. Creus, J. Panek, C. Duboc, M. Novic, D. Mathis, T. R. Ward, Artificial metal-loenzyme for enantioselective sulfoxidation based on vanadyl-loaded streptavidin, J. Am. Chem. Soc., 2008, 130, 8085-8088. 

More recently. Ward and collaborators reported that Os04-boimd wild-type streptavidin (SAV WT) catalyzed the enantioselective cis-dihydroxylation of a-methylstyrene with 95% ee (Scheme 10.8). Addition of biotin in the reaction medium or the point mutation of residue Aspl28 yielded much less selective enzymes, indicating that the catalytically active Os moiety was located in the... 

The streptavidin variant is generated as a part of a screen of modifications. In this work, no asymmetric induction was obtained without protein, and the wild-type streptavidin (Sav) gave a reduction product of up to 57 % e.e. (/ ). However, the S112A mutant of Sav gave an amine in up to 96 % e.e. (R), and in other cases (e.g. S112K mutant) the enantioselectivity could even be reversed. In addition, up to 4000 turnovers of the synthetic enzyme were able to be achieved [133-137]. Computational and molecular modelling has been applied to this process to aid optimization [138]. 

Artificial metalloenzymes based on vanadyl-loaded streptavidin was used for catalytic enantioselective sulfoxidation with f-butyl hydroperoxide [70]. Incorporation of a vanadyl ion into the biotin-binding pocket of streptavidin resulted in a catalyst that transformed both dialkyl and alkyl-aryl sulfides to their sulfoxides in high ee. 

Hydrogenation of A-acetamidoacrylate with the avidin-biotin and rhodium-diphosphine complexes shows a moderate enantioselectivity, yielding (S)-N-acetamidoalanine at41% ee (Figure 12.8). " Subsequently, an artificial metalloenzyme system using a combination of biotinylated diphosphine with mntated streptavidine was prepared. This catalytic system qnantitatively yielded highly enantioselective products ((R) = 94%). ... 

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