bioHybrids

bioHybrids






bioHybrid Systems






Metal Corroles as Heme Analogs: Cofactor Exchange on Myoglobin and Heme Oxygenasen

The exchange of non-covalently bound cofactors in proteins against synthetic metal complexes is currently in the focus of many bioinorganic research activities aiming towards the preparation and investigation of biohybride compounds and bioconjugated catalysts. The figure below provides a general graphical sketch to illustrate this approach which makes use of the properties of the natural proteinogenic material, i.e., site isolation, as well as chirality and micropolarity of the active site.

Scheme of the cofactor exchange

Schematic representation of the cofactor exchange

The most successful approach so far has been the exchange of heme in simple heme proteins, like myoglobin or horseradish peroxidase, for modified hemes or other porphyrins. As the modified metal porphyrins are structurally related to the natural heme group, novel reactivities may be introduced to the protein without significant changes at the active, heme binding pocket.

Isomeric heme analogs

Representation of isomeric propionate substituted iron corroles

Propionate substituted corroles with different central metals have been successfully prepared and introduced as cofactor analogs in different apo-myoglobins. Even copper corroles, which are not capable of binding to the histidine residue of the protein pocket, can be fully bound and appears to be robust to dissociation from the biohybrid compound. During studies of the interaction of iron corroles with various heme oxygenases (in collaboration with Nicole Frankenberg-Dinkel, Ruhr-Universität Bochum) is was found that the natural ring opening may takes place, depending on the regiochemistry of the corrole and the origin of the protein. Surprisingly, however, in this case no CO is released.

Fe-Corrole-ring opening

Unusual ring opening of γ-CH-Fe(cor) by HO-3 from Arabidopsis thalliana

Currently, we expand the portfolio of heme analogs. Further work on other heme proteins and on mutants is in progress.

  • B. Gisk, F. Brégier, R. A. Krüger, M. Bröring, N. Frankenberg-Dinkel, Biochemistry 2010, 49, 10042-10044.
  • M. Bröring, F. Brégier, O. Burghaus, C. Kleeberg, Z. Anorg. Allg. Chem. 2010, 636, 1760-1766.
  • M. Bröring, F. Brégier, R. Krüger, C. Kleeberg, Eur. J. Inorg. Chem. 2008, 5505-5512. Correction: Eur. J. Inorg. Chem. 2009, 2865.