Nucleic acids helix formation

Nucleic acid structures and sequences primary and secondary structure of DNA fragments, translocation of genes between two chromosomes, detection of nucleic acid hybridization, formation of hairpin structures (see Box 9.4), interaction with drugs, DNA triple helix, DNA-protein interaction, automated DNA sequencing, etc. 

In macromolccules with strong intramolecular interactions, a cooperative order-disorder (helix-coil) transition is possible, which is of prime importance for solutions containing proteins and nucleic acids. The formation of a system of intrsunolecular H-bonds among the groups of the main chain, stabilized by hydrophobic interactions, leads to the helix conformation. As temperature rises, or an active solvent is introduced, intramolecular H-bonds break down, and the helix-coil transition occurs. It is reversible with decreasing temperature or removing the active. solvent, respectively. ... 

The amino acid sequence of our first aPNA (which we termed backbone 1 or bl) was designed based on this amphipathic hehx sequence (Fig. 5.3 B). Specifically, this aPNA backbone included hydrophobic amino acids (Ala and Aib), internal salt bridges (Glu-(aa)3-Lys-(aa)3-Glu), a macrodipole (Asp-(aa)i5-Lys), and an N-ace-tyl cap to favor a-helix formation. The C-termini of these aPNA modules end in a carboxamide function to preclude any potential intramolecular end effects. Each aPNA module incorporates five nucleobases for Watson-Crick base pairing to a target nucleic acid sequence. 

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. 

Nucleic acids are of great interest because they are the units of heredity, the genes, and because they control the manufacture of proteins and the functions of the cells of living organisms. Hydrogen bonds play an important part in the novel structure proposed for deoxyribonucleic acid by Watson and Crick.1,5 This structure involves a detailed eomplement riness of two intertwined polynucleotide chains, which form a double helix.117 The complementariness in structure of the two chains was attributed by Watson and Crick to the formation of hydrogen bonds between a pyrimidine residue in one chain and a purine residue in the other, for each pair of nucleotides in the chains. 

Tn orcTer to extend these conformational energy studies to the analysis of multi-stranded nucleic acid systems, it is necessary to devise a procedure to identify the arrangements of the polynucleotide backbone that can acconmodate double, triple, and higher order helix formation. As a first step to this end, a computational scheme is offered here to identify the double helical structures compatible with given base pairing schemes. 

The above potential energy method provides a convenient way to identify directly those conformations of the nucleic acid backbone and base that can participate in double helix formation. 

Melting and helix formation of nucleic acids are often detected by the absorbance of ultraviolet light. This process can be understood in the following way The stacked bases shield each other from light. As a result, the absorbance of UV light whose wavelength is 260 nanometers (the Amo) of a double-helical DNA is less than that of the same DNA, whose strands are separated (the random coil). This effect is called the hypochromicity (less-color) of the double-helical DNA. 

RNA but of both handednesses. Upon appending a single homochiral residue such as L-lysine at the carboxy terminus of the helix, the peptide nucleic acid polymers predominantly fold into duplexes of a single handedness. This phenomenal positive cooperativity can be considered a form of molecular amplification. Additional examples on spontaneous and induced formations of helical morphologies were reviewed [114,182]. 

The NMR studies of nucleic acids can yield information about base sequences, conformations in solution, helix formation, and hydrogen bonding between base pairs. 

This type of hydrogen bonds includes the N-H 0=C interactions which are the most predominant hydrogen bonds in fibrous and globular proteins. Because they are responsible for the formation of the commonly occurring secondary structure elements a-helix, -pleated sheet and / -turn, a large body of much less accurate data is available from protein crystal structures which will be analyzed in Part III, Chap. 19. The N-H 0=C type hydrogen bond is also the most common in the purine and pyrimidine crystal structures (Thble 7.14), and is one of the two important bonds in the base pairing of the nucleic acids. 

An electrochemical DNA hybridization biosensor basically consists of an electrode modified with a single stranded DNA called probe [109]. Usually the probes are short oligonucleotides (or analogues such as peptide nucleic acids). The first and most critical step in the preparation of an electrochemical DNA biosensor is the immobilization of the probe sequence on the electrode. The second step is the hybrid formation under selected conditions of pH, ionic strength and temperature. The next step involves the detection of the double helix... 

This helicate formation mechanism can be extended to interactions with other materials. In the example shown in Fig. 4.2, hgands carrying nucleobases are used. The helicate forms a helical structure similar to the double helix of DNA, where the nucleobases in the helicate are on the outside of the helix. This helixate can form complexes with actual nucleic acid through complementary base pairing. The artificial supramolecular complex can read the programs of naturally-occurring molecules. 

Since the structure of DNA was first revealed by Watson and Crick in 1953, the formation of the double helix of nucleic acids by a self-directing, co-operative process has fascinated several generations of scientists. In general terms, DNA may be seen to self-assemble by a process in which two long chain polytopic receptors interact with the base pairs in such a way that each association step sets the stage for the one that follows. 

There are important differences between the two nucleic acids. DNA has two long chains, or strands, of nucleotides that mirror each other and which are arranged in a double helix format. RNA has a single strand. Furthermore, the four bases of the nucleotides of DNA are adenine, cytosine, guanine, and thymine, while those of RNA lack thymine, which is substituted by uracil. The DNA, copies of which are found in every cell of the... 

---