Metals, peptide ligand interactions

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. 

Pioneering work in this area was aimed at using specific metal ligand interactions to induce and stabilize secondary structures. This has been achieved by Ghadiri et al. for a-helical structures through the formation of transition metal and Ru(II) inert complexes with two imidazoles of His or one thiol of Cys and one imidazole of His in i, i + 3 or i, i + 4 relationships.1[37,38 In almost all cases the helix content and stability increased upon metal complexation, especially with i, i + 4 peptides. This work resembles the stabilization of helical structures using metal complexation by EDTA-like side chains discussed in Section 9.4.6. 

The detailed structural study of metalloproteins was preceded by the study of small molecule metal complexes of amino adds and peptides [478]. The development of force fields for modeling metalloproteins might, logically, also begin with molecular mechanics modeling of amino acid and peptide complexes that have metal-ligand interactions of the type seen in the metalloprotein of interest. In this way, force-field... 

Fc-functionalized amino acids and peptides have received some attention as metal binding ligands (Scheme 5.3). Chohan has shown from spectroscopic evidence that l.l -dimethyl-Fc derivatives of amino acids formed square planar metal complexes with Cu(ll) 8, whereas with Co(ll) and Ni(ll) octahedral metal complexes of 9 were formed. [24]. Electrochemical detection of metal ion interaction was demonstrated by Hirao, who showed that the electrode potential of Fc-peptide 10 shifted cathodically by 20mV when complex 11 was formed [25]. 

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