Peptides heme systems

While these complex model heme proteins have a large potential for functionalization, an interesting approach that is very different has been taken by other workers in that the heme itself functions as the template in the formation of folded peptides. In these models peptide-peptide interactions are minimized and the driving force for folding appears to be the interactions between porphyrin and the hydrophobic faces of the amphiphiUc peptides. The amino acid sequences are too small to permit peptide-peptide contacts as they are separated by the tetrapyrrole residue. These peptide heme conjugates show well-re-solved NMR spectra and thus well-defined folds and the relationship between structure and function can probably be determined in great detail when functions have been demonstrated [22,23,77]. They are therefore important model systems that complement the more complex proteins described above. 

The use of disulfide linked di-a-helical peptides for the self-assembly of a heme-peptide model compounds has also been explored by Benson et al. (109). Conceptually analogous to the larger heme-protein systems utilized by Dutton and co-workers, to be detailed later, the incorporation of C4 S5mimetric Co(III)-porphyrins, based on coproporphyrin and octaethylporphyrin, resulted in helical induction comparable to that observed in the covalent PSM systems. 

These minimalistic peptide scaffolds potentially provide a biologically relevant laboratory in which to explore the details of heme-peptide interactions and, with development, perhaps approach the observed range of natural heme protein fimction. These heme-peptide systems are more complex than typical small molecule bioinorganic porphyrin model compoimds, and yet are seemingly not as enigmatic as even the smallest natural heme proteins. Thus, in the continuum of heme protein model complexes these heme-peptide systems lie closer to, but certainly not at, the small molecule limit which allows for the effects of single amino acid changes to be directly elucidated. 

In the smaller peptide systems, only three reports containing heme peptide reduction potentials have been published however, this limited data set reveals two important aspects of cytochrome design. Figure 12 shows that Huffman et al. (125) have convincingly illustrated a direct... 

In contrast to the peptide systems, there exists a somewhat more robust literature on the electrochemistry of hemes in the larger protein systems that provides a wealth of insight into how proteins modulate the reduction potential of heme cofactors. A variety of groups have reported the reduction potential of various hemes in four-a-helix bimdle architectures, which is beginning to reveal the fundamental factors that control heme reduction potentials. 

The energetics of peptide-porphyrin interactions and peptide ligand-metal binding have also been observed in another self-assembly system constructed by Huffman et al. (125). Using monomeric helices binding to iron(III) coproporphyrin I, a fourfold symmetric tetracarboxylate porphyrin, these authors demonstrate a correlation between the hydropho-bicity of the peptide and the affinity for heme as well as the reduction potential of the encapsulated ferric ion, as shown in Fig. 12. These data clearly demonstrate that heme macrocycle-peptide hydrophobic interactions are important for both the stability of ferric heme proteins and the resultant electrochemistry. 

The interaction of dioxygen has been observed in several systems, mostly due to autooxidation of ferrous hemes with dioxygen, but only characterized in a few instances. Sakamoto et al. (119) have illustrated peroxidase-type activity using a helix-disulfide-helix system that binds a single heme as shown in Fig. 13. The initial communication illustrated that the addition of an organic cosolvent, trifiuoroethanol, increases the helical content of the peptide, the affinity for heme (1.7 DM IQ at maximal affinity, 15% TFE), and the peroxidase activity (conversion of... 

Electron-transfer in biological systems takes place through the mediation of a number of proteins, which contain a variety of active sites such as heme, Fe—S, Cu, and flavin. These active sites are protected from the solvent by a hydrophobic environment created by the peptide chain 48). The redox potential of a biological redox couple in vivo lies, for the most part, between —0.5 and +0.85 V. The former and latter potentials correspond to the redox potentials of H20/H2 and H20/02 respectively 49). 

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