Nucleic acid double helix structure

The hydrophobic effect stabilizes the three-dimensional structures of macromolecules. In the nucleic acid double helical structures, the hydrophobic bases are stacked along the helix axis and shielded from solvent by the hydrophilic sugar-phosphate backbone, which is heavily hydrated. A comparable scheme is found in many crystal structures of nucleosides and nucleotides, where the bases are stacked... 

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). 

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. 

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. 

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). 

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... 

Hydrogen-bonding interactions are considerably weaker than ionic interactions and covalent bonds but have a profound effect on many chemical and physical properties [221] and determine the shapes of large molecules such as proteins and nucleic acids. Protein secondary structure is determined by H bonding between the carbonyl oxygen of one amide unit and the N—H bond of another. The two strands of the double helix of... 

The molecule of DNA is like a coded message. This message, the genetic information contained in and transmitted by nucleic acids, depends on the sequence of bases from which they are composed. It is somewhat like the message sent by telegraph, which consists only of dots, dashes, and spaces in between. The key aspect of DNA structure that enables storage and replication of this information is the famed double helix structure of DNA mentioned above. 

The mRNA is known as the sense strand because it is the portion of the DNA that is ultimately translated by the cell into proteins. An antisense strand is the other, complementary strand in DNAs double helix structure—or any nucleic acid that is complementary to, and can pair exactly with, at least part of a sense strand. 

The structure of the DNA molecule is basically determined by nucleic acid base interactions. Although the three-dimensional double helix structure of DNA is influenced by various contributions, the hydrogen bonding in DNA base pairs is of particuar importance. Because it is difficult to obtain gas phase experimental data for isolated base pair characterisation (only a limited number of experimental studies are available [21]) quantum chemical calculations can represent a useful tool to obtain reference data on the structure, properties and interactions of nucleic acid pairs. Theoretical studies can help us to understand the properties of nucleic acids and they are fundamental for verification... 

Figure 1.5 Diagrammatic representation of (a) a nucleic acid and (b) double helix structure of DNA. Illustrations, Irving Geiss. Rights owned by Howard Hughes Medical Institute. Reproduction by permission only.

James Watson and Francis Crick put together these two pieces of information in their famous 1953 proposal of a double-helix structure for DNA. They concluded that DNA consists of two interacting helical strands of nucleic acid polymer (Fig. 23.24), with each cytosine on one strand linked through hydrogen bonds to a guanine on the other and each adenine to a thymine. This accounted for the observed molar ratios of the bases, and it also provided a model for the replication of the molecule, which is crucial for passing on information during the... 

Polynucleotide (nucleic acid) strands link to each other in pairs to form the well-known double helix structure (see Text Fig. 19.30). 

Watson, James D., and Francis H. C. Crick. Molecular Structure of Nucleic Acids. A Structure for Deoxyribose Nucleic Acid. Nature 171 (1953) 737-78. This is the epochal paper disclosing the double-helix structure of DNA. 

Genetic material for the protocell will be supplied by peptide nucleic acid, or PNA, which has the same double-helix structure and the same four chemical bases as DNA, but has a peptide backbone. A light-sensitive molecule will be able to provide the energy to convert precursor molecules into new fatty acids and PNA molecules. 

Although their P content was recognised at an early date, the most significant features of the nucleic acid constitution were not unravelled until 1953, when Crick and Watson [18] proposed the now celebrated double helix structure. This was confirmed by x-ray analysis carried out by Wilkins and Franklin [19]. About a decade earlier Avery and co-workers [20,20a] had resolved the role of the nucleic acids as the carriers of genetic information, and these two discoveries have together laid the foundations of modem genetics (Chapter 11.6). 

Fig. 9.3 Three-dimensional structures of nucleic acid double helices, (a) DNA B-form double helix, (b) RNA A-fram double helix (Reproduced with permissitm fiom Saenger W (1984) Principles of nucleic add structure. Springer-Verlag, New York. Figs. 10.1 and 11.3, pp 244,262)...

The overall aim is usually to determine the complete 3D structure of a nucleic acid and this is achieved in the same fashion as for protein structures. Thus, the NMR spectra are interpreted in terms of qualitative or semi-quantitative distance information which is then used as a set of constraints for a theoretical calculation of the structure generally based on distance geometry or restrained molecular dynamics calculations. One of the main problems with this approach, unlike for proteins, is the lack of long-range distance constraints for double-helix structures. 

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