Nucleobases sites

The use of nonbiological nucleobases to enhance oligonucleotide duplex stability is widespread, and an exhaustive exploration of this field is beyond the scope of this review. At the same time, recent studies exist that go beyond this goal with the aim of understanding the function of base interactions in duplex stability and the impact of unusual nucleobases on both conformation and assembly. Herein, we focus on a few of these examples as representatives of the field and to highlight how modifications at nucleobase sites that are remote from the backbone can have profound architectural effects on... 

There has also been considerable interest in the use of MS/MS to sequence oligonucleotides. In a similar fashion to peptides, oligonucleotides possess both basic (i.e., the nucleobase sites) and acidic (i.e., the phosphate sites) functional groups. They readily form [M + H]+ and [M - H] ions under ESI conditions, which can be subjected to CID to yield the partial to complete sequence information. The sequence ion nomenclature of McLuckey [43] has gained widespread acceptance (Scheme 11). 

Comparisons between MS/MS of the (M - HJ- and /M + H]+ Ions of Oligpdeoxynudeotides. Under low-energy CID conditions in the ion-trap, similar classes of ions, such as the base loss nonsequence and the wn sequence ions, are observed in the MS/MS spectra of both the [M - H] and [M + H]+ ions [44]. The key physical organic concepts discussed above can readily be used to provide mechanistic rationals for these fragmentation reactions. For the M + H]+ ions the most likely site of protonation is at the nucleobase sites, which have the higher proton affinity. Thus protonation at these sites acts as a trigger for neutral base loss via El or intramolecular E2 mechanisms [44]. The order of nucleobase loss for the [M + H]+ ions is C > G > A > T. In contrast, for the... 

Polynucleotides accommodate four different nucleobase sites or message units. They offer enormous diversity by extended sequences, for example,. .. GUAGUGCGUCGG. In a parallel way, molecules offer a richness of ABA-contact sequences. ..(C-C)(C-H)(C-H)(C-C)... and thus electronic messages. As... 

A series of amine-tethered nucleobases such as 8 has also been developed. These ligand systems have allowed the interaction of d-block metal ions with the N3pUrine site to be probed and an indication of base-specific metal-ion binding has begun to emerge (55-58). 

There is an extensive number of nucleobase complexes that contain multiple metal ions (75). In some cases the binding sites are in close proximity and there is the possibility for metal-metal interactions. Figures 23 and 24 illustrate various binding modes involving the N,0-donor sites which can potentially give rise to such phenomena. 

A unique aspect of the G-quartets 34 and 16 is that their assembly involves only metal-ligand bond formation. Since the sites on the nucleobase involved in coordination are either N7 or [N7 + N3] this... 

The effect of the aqueous medium on the reactivity and on the stability of the resulting adducts has been investigated to assess which adduct arises from the kinetically favorable path or from an equilibrating process. The calculations indicate that the most nucleophilic site of the methyl-substituted nucleobases in the gas phase is the guanine oxygen atom, followed by the adenine N1, while other centers exhibit a substantially lower nucleophilicity (see activation Gibbs energies in Table 2.2). 

Although the reduction potentials of DNA bases and UV induced DNA lesions inside a DNA double strand or inside the active site of a DNA photolyase, together with the reduction potential of the photoexcited FADH- in the photolyases, are not known, currently available redox potentials indicate that the single electron reduction of a nucleobase or a UV induced dimer lesion by a reduced and deprotonated flavin coenzyme is a weakly exothermic process. The reduced and deprotonated FADH- in its photoexcited state is... 

Incorporation of an artificial flavin nucleobase and of a cyclobutane pyrimidine dimer building block into DNA DNA double strands, DNArPNA hybrid duplexes, and DNA-hairpins, provided compelling evidence that an excess electron can hop through DNA to initiate dimer repair even at a remote site. The maximum excess electron transfer distance realised so far in these defined Donor-DNA-Acceptor systems is 24 A. New experiments are now in progress to clarify whether even larger transfer distances can be achieved. 

The availability of different metal ion binding sites in 9-substituted purine and pyrimidine nucleobases and their model compounds has been recently reviewed by Lippert [7]. The distribution of metal ions between various donor atoms depends on the basicity of the donor atom, steric factors, interligand interactions, and on the nature of the metal. Under appropriate reaction conditions most of the heteroatoms in purine and pyrimidine moieties are capable of binding Pt(II) or Pt(IV) [7]. In addition, platinum binding also to the carbon atoms (e.g. to C5 in 1,3-dimethyluracil) has been established [22]. However, the strong preference of platinum coordination to the N7 and N1 sites in purine bases and to the N3 site in pyrimidine bases cannot completely be explained by the negative molecular electrostatic potential associated with these sites [23], Other factors, such as kinetics of various binding modes and steric factors, appear to play an important role in the complexation reactions of platinum compounds. 

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... 

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