Nucleic double helix

Copper(I) tends towards a tetrahedral coordination geometry in complexes. With 2,2 -bipyr-idine as a chelate ligand a distorted tetrahedral coordination with almost orthogonal ligands results. 2,2 -Bipyridine oligomers with flexible 6,6 -links therefore form double helices with two 2,2 -bipyridine units per copper(I) ion (J. M. Lehn, 1987,1988). J. M. Lehn (1990 U. Koert, 1990) has also prepared such helicates with nucleosides, e.g., thymidine, covalently attached to suitable spacers to obtain water-soluble double helix complexes, so-called inverted DNA , with internal positive charges and external nucleic bases. Cooperative effects lead preferentially to two identical strands in these helicates when copper(I) ions are added to a mixture of two different homooligomers. 

H bonding also vitally influences the conformation and detailed structure of the polypeptide chains of protein molecules and the complementary intertwined polynucleotide chains which form the double helix in nucleic acids.Thus, proteins are built up from polypeptide chains of the type shown at the top of the next column. 

F. H. C. Crick. J. B. Watson and M. H. F. Wilkins (with Rosalind Franklin) establish the double helix structure of nucleic acids (Nobel Pnze 1962). 

WiTTUNG P., Nielsen P. E., Buchardt O., Egholm M., Norden B. DNA-like double helix formed by peptide nucleic acid. Nature 1994, 368 561-563. 

N. T., Lhomme J., Helene C. Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an oligo-[alpha]-thymidylate covalently linked to an azidoproflavine derivative. Nucleic Acids Res. 1987 15 7749-7760. 

The term peptide nucleic acids was chosen because of the peptide bond in the polymer (see Sect. 5.2). The bond between the polyamide strand and the organic bases involves an acetyl group. The formation of DNA-like double helix structures by PNAs was described by Pernilla Wittung et al. (1994). The question arises as to whether peptide nucleic acids can in fact be synthesized under prebiotic conditions. 

Base pair (bp) The four nucleotides in the DNA contain the bases adenine (A), guanine (G), cytosine (C), and thymine (T). Two bases (adenine and thymine or guanine and cytosine) are held together by weak bonds to form base pairs. The two strands of human DNA are held together in the shape of a double helix by those bonds between base pairs. For example, the complementary nucleic acid base sequence to G-T-A-C that forms a double-stranded structure with the matching bases is C-A-T-G. 

Anin, M.F., Gaucheron, F., and Leng, M. (1992) Lability of mono functional cis platinum adducts Role of DNA double helix. Nucleic Acids Res. 20, 4825-4830. 

In the last example, we move to the general problem of nucleic acid simulations. It is abundantly clear that simulations on DNA double helix... 

Fig. 16. An unusual interrupted helix from subtilisin (residues 62-86), in which the helical hydrogen bonds continue to a final tum that is formed by a separate piece of main chain. Such interrupted helices (broken on one side of the double helix) are apparently a fundamental feature of nucleic acid structure as illustrated by tRNA, but are exceedingly rare in protein structure.

The influence of DNA on the photo-electron transfer process between a variety of donor-acceptor couples has been examined during the last ten years. For all the systems studied, the metal complex interacts with the DNA and plays the role of electron acceptor or donor in the hydrophobic DNA microenvironment, whereas the other partner of the process, i.e. the reducing or oxidising agent in the ground state, is localised either on the DNA double helix, or does not interact with the nucleic acid and remains in the aqueous phase. Thus three... 

The protection of a reactive intermediate complex by the DNA double helix versus a neutral oxidising agent in solution, has also been demonstrated by studying a photo-electron transfer process. In this example the intermediate complex is produced photochemically on the DNA, and is examined spectroscopically after a laser pulsed excitation [73]. Thus Ru(TAP)2(HAT) physically bound to nucleic acid is photo-reduced by hydroquinone during the laser pulse. The intermediate [Ru(TAP)2(HAT)] so-produced, detected by its absorption at 480 nm, is reoxidised by benzoquinone purposely added as oxidant to the solution. It is shown that this reoxidation of the mono-reduced complex is slower in the presence of polynucleotide than in its absence, indicating a protection of the transient mono-reduced complex in the DNA grooves. 

The role of DNA in storing and transferring genetic material is dependent on the properties of the four bases. These bases are complementary in that guanine is always associated with cytosine, and adenosine with thymine. Watson and Crick, some 40 years ago, showed that the stability of DNA is due to the double helix structure of the molecule that protects it from major perturbations. Information is ultimately transferred by separating these strands which then act as templates for the synthesis of new nucleic acid molecules. 

The nucleic acids known as deoxyribonucleic acid (DNA) are the molecules that store genetic information. This information is carried as a sequence of bases in the polymeric molecule. Remarkably, the interpretation of this sequence depends upon simple hydrogen bonding interactions between base pairs. Hydrogen bonding is fundamental to the double helix arrangement of the DNA molecule, and the translation and transcription via ribonucleic acid (RNA) of the genetic information present in the DNA molecule. 

The tertiary structure of DNA is the structural level that is most relevant to 3-D reality. Traditionally, ODNs in a physiologically relevant aqueous solution are considered to be in a random-coiled ssDNA state or in the form of dsDNA helix in the presence of a complementary DNA, including the case of self-complementarity. The double helix is the dominant tertiary structure for biological DNA that can be in one of the three DNA conformations found in nature, A-DNA, B-DNA, and Z-DNA. The B-conformation described by Watson and Crick (11) is believed to predominate in cells (12). However other types of nucleic acid tertiary structures different from random or classical double-stranded helix forms can also be observed. Among them are triplexes, quadruplexes, and several other nucleic acid structures (13, 14). 

Melting Temperature. The double helix of polynucleotides described above becomes thermodynamically unstable at particular temperatures (with specified conditions of solute concentration, pH, etc.) and is transformed into the open random-coil arrangement. This transformation is rather sharp, and can be measured by the concurrent changes in a number of physical properties of the nucleic acid, such as the optical absorption coefficient. The midpoint of the transition region is called the melting point. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

There are other ways in which nucleic-acid-related compounds could be exploited as therapeutics. A new, emerging area concerns the application of RNA as a dmg. The discovery of catalytic RNA (ribozymes) by Cech and Altman was a fundamental advance in nucleic acid chemistry. According to traditional double helix dogma, RNA was a passive information-transmitting molecule. The identification of ribozymes enabled the conceptual advance that RNA can also act as a catalyst for the following biochemical processes ... 

As with proteins, the nucleic acid polymers can denature, and they have secondary structure. In DNA, two nucleic acid polymer chains are twisted together with their bases facing inward to form a double helix. In doing so, the bases shield their hydrophobic components from the solvent, and they form hydrogen bonds in one of only two specific patterns, called base pairs. Adenine hydrogen bonds only with thymine (or uracil in RNA), and guanine pairs only with cytosine. Essentially every base is part of a base pair in DNA, but only some of the bases in RNA are paired. The double-helix structure... 

Fig. 26. Nucleic acid structures. A The structure of the four bases in DNA, guanine (G), cytosine (C) adenine (A) and thymine (T). Uracil (U) replaces thymine (T) in RNA. B The spontaneous attraction of A for T and C for G allows the recognition of homologous sequences in aqueous solutions and the strong and specific hybridization of one sequence with its homologous sequence. C DNA forms a double helix at body temperature, which can be denatured to separate the strands by heating. D single stranded mRNA structure.

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