Purine base structure

Four Other derivatives related to agelasines should be mentioned. The first three differ from agelasines by the presence of a hydroxyl group at the jimction of the A and B rings, and by a modification of the purine base structure. The fourth derivative has the same thelepogane skeleton as nakamurol A (Iwagawa et al., 1998). 

These relationships are general. Hydroxyl-substituted purines and pyrimidines exist in their keto forms fflnino-substituted ones retain structures with an anino group on the ring. The pyrimidine and purine bases in DNA and RNA listed in Table 28.1 follow this general rule. Beginning in Section 28.7 we ll see how critical it is that we know the correct tautomeric forms of the nucleic acid bases. 

The analogs of pyrimidine and purine bases can be derived by purely formal structural modifications or, more rationally, from the results of biochemical investigation. 

An important group of antimetabolites are the aza analogs of pyrimidine and purine bases which are theoretically derived by a replacement of the methine group of a pyrimidine or purine nucleus with a nitrogen atom. This replacement represents a relatively minor alteration of the structure of these substances as it does not change the functional groups, practically preserves the molecular weight, and produces almost isosteric compounds. The replacement of the methine... 

Saito et al. achieved the first direct confirmation of double alkylation of purine bases by azinomycin B [140]. They incubated azinomycin B with the self-comple-mentary DNA duplex d(TAGCTA)2 and monitored the reaction by HPLC and ion spray MS. They observed initial formation of a monoadduct that was then converted into a crosslinked bisadduct. The crosslink position was identified as between the guanine of one strand and the 5 -adenine on the other strand by thermo-lytic depurination. Further decomposition prevented structural analysis of the azi-... 

The ability of o-QM to form several metastable adducts with pyrimidine (at cytosine N3) and purine bases (at guanine N7 and adenine Nl) in water suggested that the above adducts may be exploited as o-QM carriers under mild conditions, anticipating that o-QM could actually migrate along the structure of an oligonucleotide.35... 

Nucleotides can be linked together into oligonucleotides through a phosphate bridge at the 5 position of one ribose unit and the 3 position of another. The purine bases, adenine and guanine, have two heterocyclic rings, while the pyrimidines cytosine, thymine, and uracil have one. The structure of adenosine monophosphate is shown in Figure 11. 

Figure 11-8. Structures of representative conical intersections Sj/Sq in the purine bases, 9H-adenine and 9H-guanine. Adenine structures (a,b) are taken from Ref. [138]. Guanine structure (c) is taken from Ref. [171]...

Figure 1.49 The structures of the common purine bases of RNA and DNA. The associated sugar groups are bound in N-glycosidic linkages to the N-9 position.

One of the most important reactions of purines is the bromination of guanine or adenine at the C-8 position. It is this site that is the most common point of modification for bioconjugate techniques using purine bases (Figure 1.53). Either an aqueous solution of bromine or the compound N-bromosuccinimide can be used for this reaction. The brominated derivatives then can be used to couple amine-containing compounds to the pyrimidine ring structure by nucleophilic substitution (Chapter 27, Section 2.1). 

Our inhibitor design strategy was based on the premise that structural modifications in the base of purine riboside that enhance purine base hydration without impairing the binding of the hydrated species to the ADA binding site would result in purine riboside (PR) analogues with high ADA inhibitory potency. Since the apparent inhibition constant (Kj (app)) is related to the hydration equilibrium constant (Keq) and the inhibitory constant for the hydrated molecule (Kj ) by... 

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. 

There are five common bases found in nucleic acids. Adenine (A), guanine (G) and cytosine (C) are found in both DNA and RNA. Uracil (U) is found only in RNA and thymine (T) only in DNA. The structures of these bases are shown in Figure 13.2. Adenine and guanine are purine bases while uracil, thymine and cytosine are the pyrimidine bases. 

The first evidence of the special structure of DNA was the observation that the amounts of adenine and thymine are almost equal in every type of DNA. The same applies to guanine and cytosine. The model of DNA structure formulated in 1953 explains these constant base ratios intact DNA consists of two polydeoxynucleotide molecules ( strands ). Each base in one strand is linked to a complementary base in the other strand by H-bonds. Adenine is complementary to thymine, and guanine is complementary to cytosine. One purine base and one pyrimidine base are thus involved in each base pair. 

DNA has only a limited stability in the temperature and pH conditions of an organism. Spontaneous changes in the DNA structure may occur and cleavage of purine bases is assigned an important role. The apurinic sites resulting from depurination may give rise to mutations if not repaired. 

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