Studies on Oligonucleotides

The study of higher order oligonucleotides has usually been undertaken to study the effect of sequence on the GG link. As pointed out from the restriction endonuclease studies, the sequence on either side of the GG link can be a determining factor in reactivity, since the sequence will dictate local conformation, etc. These studies are of particular interest now that the detailed geometry of the GG link is known and the results can be discussed in this context to give an understanding of the overall nature of the localized distortion on the DNA. 

Platinated oligonucleotides can, however, form duplexes with complementary strands. The octanucleotide d(GpApTpCpCpGpGpC) was platinated and shown to form a duplex with its complementary decanucleotide [99]. These conclusions are in agreement with studies on the decanucleo- 

Molecular mechanics calculations for the platinated double stranded oligonucleotides d(GpGpCpCpGpGpCpC)—d(CpCpGpGpCpCpGpG) 

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During studies on oligonucleotide formation with excess l-(mesitylene-2-sulfonyl)-l, 2,4-triazole (MSNT) or tetrazole, Reese discovered that protected uridines are converted at room temperature into the chemically stable 1,2,4-triazole derivatives in high yields (80MII). Reese... 

Over the last few years, significant advances in the depth of understanding of the conformational features of the polynucleotide—platinum complex interaction have come from both solution (CD, NMR) and solid-state (X-Ray) studies on oligonucleotide fragments, particularly dinucleotide complexes. Excellent summaries of the status of model studies and their relationship to the molecular mechanism of cisplatin can be found in references [82 and 141]. These complement the earlier reviews [83, 84]. The features outlined do in fact confirm some of those expected from model studies, although there has not been an extensive comparison with the trans-isomcr. 

Unfortunately the extensive studies on oligonucleotides using PDMS refer to protected synthetic oligomers and a detailed discussion of them is therefore outside the scope of this Review. However an exciting pointer to future developments is the observation 24) of the molecular ion for a dimer (w/z 12637) of a protected dodecanucleotide, which points to the possible use of PDMS to detect duplex formation in oligonucleotides from native DNA and RNA. 

In Section II we provide an overview of the current status of nucleic acid simulations, including studies on small oligonucleotides, DNA, RNA, and their complexes with proteins. This is followed a presentation of computational methods that are currently being applied for the study of nucleic acids. The final section of the chapter includes a number of practical considerations that may be useful in preparing, performing, and analyzing MD simulation based studies of nucleic acids. 

Oligonucleotides with modified sugar components are another alternative to PNAs work in this direction was begun by Albert Eschenmoser, a famous synthetic chemist who was interested in the question as to why nature chose certain biomolecules for the processes of life and not others (Eschenmoser, 1991). This group carried out studies on the sugar components of the nucleic acids, in order to find out why D-ribose was used rather than another sugar. 

Although structural studies on various platinated oligonucleotides clearly demonstrate the preponderance of GG and AG adducts, they do... 

This was the starting point of further studies on the formation of silver clusters in oligonucleotides, for example in a 12-mer cytosine (5 -CCCCCCCCCCCC-3 also denoted as dCi2). Using the same stoichiometry, 2 1 1 in bases Ag+ BH4, emission spectra recorded at various excitation wavelengths reveal the presence of multiple electronic transitions with emissions centered at 485 nm, 525 nm and 665 nm, this last one, from two different excitations (Fig. 3a). The evolution in time after addition of the reductant shows an isosbestic point with a decrease in the emission band at 665 nm and an increase of the bands at 500 nm, suggesting a chemical transformation between the emitters, at least at pH lower than 10... 

Several nucleotides that were more effective inhibitors than the originally tested AZT nucleotides were identified [71]. For example, the L-enantiomers of 5-fluoro-2, 3 -dideoxycytidine monophosphate and triphosphate inhibit 3 processing and strand transfer with IC50 values of 40 pM. A structure-function study on GT-containing oligonucleotides showed that both the number of quartets formed and the loop sequences between the quartets are important for activity, and that inhibitors of this type may function by interacting with the N-terminus of integrase [72]. 

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