Purine bases, properties

Characteristic Organic Structures, 9-116 PSD, definition, 12-1 to 4 psia and psig, definition, 1-40 Purine bases, properties of, 7-5 Pyrimidine bases, properties of, 7-5 Pyrophoric chemicals, safe handling, 16-1 to 12... 

Point mutations can occur when one base is substituted for another (base substitution). Substitution of another purine for a purine base or of another pyrimidine for pyrimidine is called a transition, while substitutions of purine for pyrimidine or pyrimidine for purine are called transversions. Both types of base substitution have been identified within mutated genes. These changes lead to a codon change which can cause the wrong amino acid to be inserted into the relevant polypeptide and are known as mis-sense mutations. Such polypeptides may have dramatically altered properties if the new amino acid is close to the active center of an enzyme or affects the three-dimensional makeup of an enzyme or a structural protein. These changes, in turn, can lead to change or reduction in function, which can be detected as a change in phenotype of the affected cells. 

The obvious similarity between the purine bases of DNA and pteridines, especially between guanosine and pterins, has encouraged extensive studies of the synthesis and properties of pteridine-containing nucleoside and nucleotides. Synthetic methods have naturally built upon established methods of nucleic acid synthesis. The primary property of use in applications of these compounds to DNA chemistry is fluorescence, which is very much greater for pteridines than for purines. 

The understanding of the tautomeric properties of the purine and pyrimidine bases of the nucleic acids and the determination of the electronic properties of the principal tautomers are of fundamental importance in molecular biology, in particular in connection with the theory of mutations (for general references see, e.g. refs. 1-6.) B. Pullman and A. Pullman have presented recently in these Advances3 a detailed review of the problem as it concerns the purine bases. The present paper... 

Electrochemical transduction of the hybridisation event can be classified into two categories label-based and label-free approaches. The label-based approach can be further subdivided into intercalator/groove binder, non-intercalating marker, and NP. The label-free approach is based on the intrinsic electroactivity of the DNA purine bases or the change in interfacial properties (e.g., capacitance and electron transfer resistance) upon hybridisation [49],... 

The reaction of hydrated electrons formed by radiolysis with peroxydisulfate yields the sulfate radical anion SO4 which is a strong chemical oxidant (Eqx = 2.4 V/NHE) [50, 58]. The oxidation of both purine and pyrimidine nucleotides by S04 occurs with rate constants near the diffusion-controlled limit (2.1-4.1 x 10 M s ). Candeias and Steenken [58a] employed absorption spectroscopy to investigate acid-base properties of the guanosine cation radical formed by this technique. The cation radical has a pKa of 3.9, and is rapidly deprotonated at neutral pH to yield the neutral G(-H) . Both G+ and G(-H) have broad featureless absorption spectra with extinction coefffcients <2000 at wavelengths longer than 350 nm. This has hampered the use of transient absorption spectra to study their formation and decay. Candeias and Steenken [58b] have also studied the oxidation of di(deoxy)nucleoside phosphates which contain guanine and one of the other three nucleobases by SO4 , and observe only the formation of G+ under acidic conditions and G(-H) under neutral conditions. 

The effect of Pt coordination on the acid-base properties of the purine ligands / -ethylguanine, N -methylhypoxanthine, inosine, Af -methyladenine, and trimethyladenine has been quantitatively evaluated The acidity constants of the complexes were calculated by curve-fitting procedures, using the pH (pD) dependence of the H NMR shift data. It was found that Pt coordinated to the N -site acidifies the N-7 unit to the same extent as N -coordinated Pt acidifies the N-1 site. 

Base modification at the 4-position of pyrimidines leads to loss of base-pairing properties. The thiol moiety in 91 was deprotected after ODN synthesis using 1 M DBU in acetonitrile. The modified oligothymidylate was then cleaved from the solid phase and reacted with N-(2-chloroethylthio)phthalimide to yield 92, which was subjected to further derivatization [264]. Purine base positions accessible for ligand attachment are C-8 of adenosine (93) [265] and C-2 of guanosine (94) [266]. 

Analogs of naturally occurring purine bases with antileukemic, immunosuppressant, and antiviral properties include mercaptopurine, thioguanine, azathioprine, acyclovir, ganciclovir, vidara-bine, and zidovudine. Other purine analogs important in cancer therapy include pentostatin (2 -deoxycoformycin), cladribine, and fludarabine phosphate. 

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