Enantiomeric discrimination of Ru-substrates by cytochrome P450(cam)

Molecules with photosensitizers attached to substrates (Wilker et al., Ange w. Chem. Int. Ed. 38 (1999) 90-92) or cofactors (Hamachi et al., J. Am. Che m. Sec. 121 (1999) 5500-5506) can rapidly deliver redox equivalents to buri ed active sites. The structure of cytochrome P450(cam) (P450) co-crystalliz ed with a prototypal sensitizer-substrate, [Ru-C-9-Ad]Cl-2, has been determ ined (Dmochowski et al., Proc. Natl. Acad. Sci. USA 96 (1999) 12987-12990); and, in separate UV-vis absorption and time-resolved luminescence experime nts, the binding of the Lambda and Delta enantiomers of Ru-C-9-Ad to P450 h as been measured. The results, K-D(Delta/Lambda)similar to 2, indicate that the bipyridyl ligands of the Lambda isomer interact more favorably with hy drophobic residues at the entrance to the substrate channel. We conclude th at enantiospecific interactions may be exploited in the design of enzyme-me tallosubstrate conjugates. (C) 2000 Elsevier Science S.A. All rights reserv ed.