Ligand binding, protein Macrocyclization

There is potential in the anti-HIV field. Polyoxometallates of the Keggin type bind to viral envelope sites on cell surfaces and interfere with virus adsorption. Metal-chelating macrocyclic bicyclam ligands are among the most potent inhibitors of HIV ever described, and there is considerable interest in the role of Zn proteins in the viral life cycle. 

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 binding of cyclic thioethers to metal centers has also led to the isolation of complexes in which the coordinative properties of the ligand do not lit the stereochemical preferences of the metal ion(s) (188), Thus, a series of macrocyclic thioether complexes incorporating unusual stereochemistries and/or oxidation states has been generated (188). This is linked to the biological activity of the blue copper proteins and model systems in which the coordination geometry about Cu(II) is strained [in an entatic state (.212,221)] such that the Cu(II)/(I) couple occurs at a particularly positive potential that is, the Cud) state is stabilized. The ability of cyclic thioethers to modify their coordination properties is inherent in this approach (76,108,111). 

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