Guanine coordination sites with

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

With aquated Pt(II) compounds, numerous studies have revealed the kinetic preference of the 6-oxopurine N7 site [15,35]. In addition to the favorable electrostatic potential mentioned above [23] also steric factors seem to favor coordination to the guanine N7 site, in particular [36]. Estimated relative steric parameters (in parenthesis) suggest that the guanine N7 (1.00) and hypoxanthine N7 (1.03) atoms are the least sterically hindered binding sites in alkylated nucleobases, followed by the adenine N7 (1.17) and deprotonated hypoxanthine N1 (1.17) sites and the deprotonated N3 atoms of the different pyrimidine bases (1.39 for U, 1.44 for T, and 1.56 for C), while the adenine N1 (1.58) and... 

Both Ru(II) and Ru(III) complexes are known to bind DNA preferentially at N7 of G but also to A and C bases (182, 183). Although most ruthenium antitumor agents have two reactive coordination sites, GG intrastrand cross-links on DNA do not appear to form readily. The only example appears to be the adduct of 27 with GpG, which has been structurally characterized by NMR spectroscopy (184). In this complex, the two N7-coordinated guanines adopt a head-to-head conformation and the two bases are strongly destacked. 

Cisplatin (Platinol) is an inorganic coordination complex with a broad range of antitumor activity. It is especially useful in the treatment of testicular and ovarian cancer. It binds to DNA at nucleophilic sites, such as the N7 and 06 of guanine, producing alterations in DNA structure and inhibition of DNA synthesis. Adjacent guanine residues on the same DNA strand are preferentially cross-linked. This platinating activity is analogous... 

In general terms, both steric effects and electronic factors are expected to play a role in determinating the reactivity of square-planar platinum complexes. The presence of planar amine ligands in cis- or /ran.y-Pt(anion )2 complexes and their orientation with respect to the coordination plane, as well as their substituents, can reduce the rates of DNA binding or thio binding compared to aliphatic ammine and amine complexes. Especially, substituents close to the coordination site should be expected to slow down axial substitution reactions at Pt. As there is now little doubt that DNA platina-tion is a key event (or THE key event) in the mechanism of action of platinum anticancer drugs, attention to the process of formation of the major adduct (GG) as an intrastrand cross-link between N(7) atoms of two adjacent guanine (G) residues, will remain important. 

In the DNA adducts of cisplatin the sites with AG and GG (A=adenosyl, G=guanosyl), are most frequently chelated, and the two bases are coordinated through N7 to cis-Pt in a head-to-head orientation. The conformational characteristics hardly change upon platination in fact only the deoxyribose moiety of the 5 -guanine has adopted an almost pure N-type conformation, compared to the S-type conformation in free d(GpG). 

The antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine also uses its N7 as a major binding site and forms a N7-phosphonate macrochelate (698).1833 Another antiviral analogue of 2 -deoxyguanosine, acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine) forms with Ni11 a bis-complex with two N7 coordinated in trans position to each other.1834... 

Findings with platinated DNA fragments (107-109) confirm the acidification of guanine residues upon N7 Pt coordination. In fact, changes in proton NMR (JH NMR) chemical shifts of guanine-H8 resonances are commonly used to assign binding sites in DNA. 

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