Imidazole groups metal binding

Biosorption is a rather complex process affected by several factors that include different binding mechanisms (Figure 10.4). Most of the functional groups responsible for metal binding are found in cell walls and include carboxyl, hydroxyl, sulfate, sulfhydryl, phosphate, amino, amide, imine, and imidazol moieties.4 90 The cell wall of plant biomass has proteins, lipids, carbohydrate polymers (cellulose, xylane, mannan, etc.), and inorganic ions of Ca(II), Mg(II), and so on. The carboxylic and phosphate groups in the cell wall are the main acidic functional groups that affect directly the adsorption capacity of the biomass.101... 

Since both proteins bound at pH 7.4, the result suggests that both had isoelectric point (pi) values <7.4. Furthermore, the 78.8-kDa protein bound to the IMAC spot, while the 14.9-kDa protein did not bind. This suggests that the 78.8-kDA protein had a free His imidazole group on its surface, while the 14.9-kDa protein did not have an available metal binding domain. 

The major metal-binding amino acid side chains in proteins (Gurd and Wilcox, 1956 see Voet and Voet, 1990) (Table II) are carboxyl (aspartic acid and glutamic acid), imidazole (histidine), indole (tryptophan), thiol (cysteine), thioether (methionine), hydroxyl (serine, threonine, and tyrosine), and possibly amide groups (asparagine and glutamine, although... 

The imidazole groups in histidine side chains are parts of the active sites of many enzymes. Like other basic groups in proteins they also may bind metal ions. 

The structure of bleomycin is shown in Figure 74, and contains a dithiazole group, thought to be responsible for the binding of DNA, an amino-pyrimidine-imidazole region which binds transition metal ions, and sugars. 

As another example, we prepared disubstituted cyclodextrin 35 in which one substituent was a metal-binding tren group while the other was an imidazole [122]. Zn2+ complexed to the tren group gave good rate acceleration in the hydrolysis of bound catechol cyclic phosphate 36, which was fastest when the two catalytic groups were attached to opposite sides of the cyclodextrin so they could not bind each other. The geometry of the complex led to the selective formation of product 37 rather than 38 both are formed equally by ordinary hydrolysis without the catalyst. 

Through systematic modification of the imidazole-appended 2-phenyl-aminobenzoate peptidomimetic scaffold (e.g., FTI-2148) a group at Abbott Pharmaceuticals have identified an expanded series of inhibitors that lack either the C-terminal Met carboxylate (as in compounds 14-23 of Ref. [55]) or the imidazole group (as in ABT-839) [56,70,71]. This latter compound became a clinical candidate and demonstrates that coordination to the zinc ion is not a prerequisite for potent inhibitors of FT. In place of metal-ligand (imidazole, thiol, etc.) coordination, ABT-839 exploits hydrophobic contact from the cyclohexylethyl and -butyl groups to the protein-binding pocket. For the structures of other CaaX peptidomimetics, please refer to Table 6.1. 

In order to accelerate the slow metalation, several methods have been proposed (1) use of substitution reaction of cadmium(II) or mercuty(II) porphyrin, (2) use of N-substituted porphyrins at the pyrrole nitrogen, (3) addition of aromatic heterocyclic bases such as pyridine and imidazole, (4) introduction of functional groups to bind metal ions in the vicini of the porphyrin nucleus (e. g. tetracarboxylic add "picket-fence" porphyrins) and (5) use of reducing agents such as hydroxylamine and ascorbic add in copperfll) incorporation. 

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