Purine-pyrimidine complexes

Tamasi G, Botta F, Cini R (2006) DFT-molecular modeling analysis of C-H- -N and C-H- - -S hydrogen bond type interactions in selected platinum-purine/pyrimidine complexes. J Mol Struct... 

Mixed Purine/Pyrimidine Complexes. Unfortunately, only very limited structural information is available (15, 16) for mixed purine/pyrimidine complexes of Pt(II). In fact, so far only complexes containing N(7)-bound 9-ethylguanine (or its N(l)-depro-tonated monoanion) and N(3)-bonded 1-methyIcytosine have been structurally characterized. Conformational drawings for these complexes are presented in Figure 5. 

Basically, the same dependencies of the stabilization energies on increasing atomic numbers of metal cations are observed in metal-purine-pyrimidine complexes as in previously published metal-purine species (Burda et al. 1996). Stabilization energies of complexes with divalent ions are larger than those of monovalent ions, and M-GC stabilization energies are larger than those for M-AT complexes. Both conclusions reflect the dominant role of the ion-dipole electrostatic contribution to the stabilization energy of these complexes. 

PNA targeting of duplex DNA is not limited to homopurine sequences. Under special circumstances (high negative superhelical stress) mixed purine-pyrimidine PNA-peptide conjugates can bind by duplex invasion (Fig. 4.7) [31], but such complexes are of limited stability. However, using a set of pseudo-complementary PNAs containing diaminopurine-thiouracil substitutions, very stable double duplex invasion complexes can be formed (Fig. 4.4) and the only sequence requirement is about 50% AT content. Very recently, it was also demonstrated that reasonably stable helix invasion complexes can be obtained with tail-clamp PNA comprising a short (>six bases) homopyrimidine bis-PNA clamp and a mixed sequence tail extension [32] (Fig. 4.7). 

The purine(3 -5 Ipyrimidine and the pyrimidine(3 -5 )purine phosphodiester linkages are partially resolved in the proflavine and daunomycin intercalation complexes with poly(dA-dT) with the phosphodiester at the intercalation site shifting to low field. This suggests that these intercalating agents exhibit a sequence specificity in their complexes with alternating purine-pyrimidine polynucleotides. 

In general the pyrimidines show a much lower reactivity towards the metal ions. Apparently no reaction was observed with uracil while the stability constants of Cu-cytosine are even lower than the lgJCi and gK% values of Cu(NH3)62+ (79). The high stability of the purine metal complexes can be attributed to the binding site at the imidazole residue. There the imino proton competes with the metal ion. Fig. 1 presents a model of the 2 1 complex of Cu-(adenine)%. 

More valuable information on nucleic acids has been obtained from pyrolysis data when it was possible to evaluate the nature and abundance of the purine/pyrimidine bases. The information on these bases is important for monitoring in vitro DNA synthesis [5,6], for the evaluation of chromosome modifications [7], and for the study of complex formation of DNA with cisplatin [11,12]. As indicated previously, the DIP technique was reported to be more useful for detecting the base component of the nucleic acid. However, some information on the bases can be obtained also by Curie point Py-MS, as it can be seen from the spectrum of NADPH (nicotinamide adenine dinucleotide phosphate) shown in Figure 13.2.3. The spectrum was obtained in similar conditions as spectra for DNA and RNA shown previously [8]. 

There has been considerable interest in recent years in the formation of condensed films of purine and pyrimidine bases at the solid-liquid interface. It is well recognised that non-covalent affinities between base pairs play a prevalent role in determining nucleic acid conformation and functionality. Likewise, there has been interest in the role of substrate and non-covalent intermolecular interactions in the configuration of ordered monolayers of purine and pyrimidine bases. There is also more general interest in the interaction of bases with metal surfaces and metal complexes. In the latter case it is noted that the biological role of nucleic acids and certain nucleotides are dependent on metal ions, particularly Mg, Ca, Zn, Mn, Cu and Ni. " Also certain metal complexes, notably of platinum, have the anti-tumour activity, which is linked to their ability to bind to bases on DNA. On a different note, the possibility that purine-pyrimidine arrays assembled on naturally occurring mineral surfaces might act as possible templates for biomolecular assembly has been discussed by Sowerby et al. 

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an essential enzyme required for normal folate metabolism in prokaryotes and eukaryotes. Its role is to maintain necessary levels of tetrahydrofolate to support the biosynthesis of purines, pyrimidines and amino acids. Many compounds of pharmacological value, notably methotrexate and trimethoprim, vork by inhibition of DHFR. Their clinical importance justified the study of DHFR in the rapidly evolving field of enzymology. Today, there is a vast amount of published literature (ca. 1000 original research articles) on the broad subject of dihydrofolate reductase contributed by scientists from diverse disciplines. We have selected kinetic, structural, and computational studies that have advanced our understanding of the DHFR catalytic mechanism with special emphasis on the role of the enzyme-substrate complexes and protein motion in the catalytic efficiency achieved by this enzyme. 

Conformational Properties of Purine and Pyrimidine Complexes of cis-Platinum... 

Nevertheless, these restrictions obtain for most purine and pyrimidine complexes with (NH3) Ru(III), so that this and related equations have considerable predictive power (as will be seen below.)... 

In this chapter we examine the synthesis and degradation of purines, pyrimidines, and hemes. These have complex structures, but are formed from simple precursors. All three can be synthesized in the body and have roles ranging from nucleic acids to hemoglobin. In addition to synthesis control of all three classes of compounds, a number of metabolic diseases associated particularly with purine and heme metabolism are discussed. The use of antimetabolites, as in chemotherapy, and the rationale for their use is presented. 

The double helix stability is determined by a longitudinal interaction of neighboring bases, called base stacking, which results from complex interactions ofTt-electron orbitals of the planar bases, dipole, dipole-induced dipole, London dispersion forces, and hydrophobic Interactions. The stability of base stacking is of the order purine-purine > purine-pyrimidine > pyrimidine-pyrimidine. The G/C pairs are more stable than A/T pairs, because they have three hydrogen bonds as opposed to two (Fig. 6.7). Therefore, stacked dimers high in G/C content are energetically preferred to those rich in A/T content (13). 

T. J. Kistenmacher and L. G. Marzilli, Chelate Metal Complexes of Purines Pyrimidines and Their Nucleosides Metal-Ligand and Ligand-Ligand Interactions. Jerusalem Symp. Quantum Chem. Biochem. 9(1), 7-40 (1977). 

Nucleic acid nu- kle-ik- [fr. their occurrence in cell nuclei] (1892) n. A family of macromolecules, of molecular masses ranging upward from 25,000, found in the chromosomes, nucleoli, mitochondria, and cytoplasm of all cells, and in viruses in complexes with proteins, they are called nu-cleoproteins. On hydrolysis they yield purines, pyrimidines, phosphoric acid, and a pentose, either D-ribose or D-deoxyribose from the last, the nucleic acid derive their more specific names, ribronucleic acid and deoxyribonucleic acid. Nuclear acids are liner (i.e., unbranched) chains of nucleotides in which the 5 -phosphoric group of each one is esterified with the 3 -hydroxyl of the adjoining nucleotide. Black JG (2002) Microbiology, 5th edn. John Wiley and Sons Inc., New York. 

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