Cisplatin lysozyme

Fig. 6 Crystal structures of metal-drug/protein composites, a cisplatin/SOD, b cisplatin/lysozyme, and c Ru complex/Pim-1 taken from PDB ID 2AEO, 2I6Z, and 2BZI, respectively...

A second family of carbohydrate-degrading enzymes, the lysozymes, produces synergistic antimetastatic activity when co-adrninistered with cisplatin [15663-27-1] to mice whose primary tumor had been surgically removed (51). 

For the construction of artificial metalloproteins, protein scaffolds should be stable, both over a wide range of pH and organic solvents, and at high temperature. In addition, crystal structures of protein scaffolds are crucial for their rational design. The proteins reported so far for the conjugation of metal complexes are listed in Fig. 1. Lysozyme (Ly) is a small enzyme that catalyzes hydrolysis of polysaccharides and is well known as a protein easily crystallized (Fig. la). Thus, lysozyme has been used as a model protein for studying interactions between metal compounds and proteins [13,14,42,43]. For example, [Ru(p-cymene)] L [Mn(CO)3l, and cisplatin are regiospecificaUy coordinated to the N = atom of His 15 in hen egg white lysozyme [14, 42, 43]. Serum albumin (SA) is one of the most abundant blood proteins, and exhibits an ability to accommodate a variety of hydrophobic compounds such as fatty acids, bilirubin, and hemin (Fig. lb). Thus, SA has been used to bind several metal complexes such as Rh(acac)(CO)2, Fe- and Mn-corroles, and Cu-phthalocyanine and the composites applied to asymmetric catalytic reactions [20, 28-30]. 

At variance, a more classical chemical environment was found for the pla-tinum(II) center in the cisplatin-hen egg white lysozyme (HEWL) species (Figure 9.6B), where platinum was found to bind to the Ns of His 15 of HEWL, two ammonia molecules in the cisplatin and another one possibly to be loosely bound water molecule. No more significant modifications of the electron density map of the protein surface were observed, ruling out the presence of additional binding site, for example, the two methionine residues (Met-12... 

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