Nucleic acid free bases

J.E. Koehne, H. Chen, A.M. Cassell, Q. Ye, J. Han, M. Meyyappan and J. Li, Miniaturised multiplex label-free electronic chip for rapid nucleic acid analysis based on carbon nanotube nanoelectrode arrays, Clin. Chem., 50... 

Miniaturized multiplex label-free electronic chip for rapid nucleic acid analysis based on carbon nanotube nanoelectrode arrays. Clin. Chem., 50,1886-1893. 

DNA polymerase enzymes all synthesize DNA by adding deoxynucleotides to the free 3 -OH group of an RNA or DNA primer sequence. The identity of the inserted nucleotide is deterrnined by its abiHty to base-pair with the template nucleic acid. The dependence of synthesis on a primer oligonucleotide means that synthesis of DNA proceeds only in a 5%o V direction if only one primer is available, all newly synthesized DNA sequences begin at the same point. 

Orozco, M. Colominas, C. Luque, F. J., Theoretical determination of the solvation free energy in water and chloroform of the nucleic acid bases, Chem. Phys. 1996, 9, 209-678. 

Cieplak, P., Caldwell, J. W., Kollman, P. A., Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation aqueous solution free energies of methanol and IV-methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases, J. Comput. Chem. 2001, 22, 1048-1057... 

J. Wang, M. Jiang, A. Fortes, and B. Mukherjee, New label-free DNA recognition based on doping nucleic-acid probes within conducting polymer films. Anal. Chim. Acta 402, 7-12 (1999). 

Solvation Free Energies of Nucleic Acid Bases and Amino Acid Side-Chains... 

Figure 3. Nucleic acid bases used in solvation free energy calculations.

A. H. Elcock and W. G. Richards, Relative hydration free energies of nucleic acid bases,... 

J. L. Miller and P. A. Kollman, Solvation free energies of the nucleic acid bases, J. Phys. 

The concept of the similarity of molecules has important ramifications for physical, chemical, and biological systems. Grunwald (7) has recently pointed out the constraints of molecular similarity on linear free energy relations and observed that Their accuracy depends upon the quality of the molecular similarity. The use of quantitative structure-activity relationships (2-6) is based on the assumption that similar molecules have similar properties. Herein we present a general and rigorous definition of molecular structural similarity. Previous research in this field has usually been concerned with sequence comparisons of macromolecules, primarily proteins and nucleic acids (7-9). In addition, there have appeared a number of ad hoc definitions of molecular similarity (10-15), many of which are subsumed in the present work. Difficulties associated with attempting to obtain precise numerical indices for qualitative molecular structural concepts have already been extensively discussed in the literature and will not be reviewed here. 

Orotic acid readily forms dimers even when irradiated in liquid medium [582, 583]. 5-Bromouracil (5-BrU) in DNA is dehalogenated, rather than forming cyclobutane-type dimers. Such DNA derivatives are more sensitive to ultraviolet irradiation than normal DNAs [584-594], Irradiation of 5-bromo-uracil and derivatives in aqueous medium produces 5,5 -diuracil [590, 591]. However, derivatives such as 3-sbutyl-5-bromo-6-methyluracil have been reported to yield cyclobutane dimers either by irradiation of frozen aqueous solutions, or by catalysis with free radical initiators, such as aluminium chloride, ferric chloride, peroxides or azonitriles [595]. 5-Hydroxymethyluracil is reported to dimerize very slowly in frozen water at 2537 A [596]. The fundamental research in the photochemistry of the nucleic acids, the monomeric bases, and their analogues has stimulated new experiments in certain micro-organisms and approaches in such diverse fields as template coding and genetic recombination [597-616]. 

The kinetics and mechanisms of the oxidation of DNA, nucleic acid sugars, and nucleotides by [Ru(0)(tpy)(bpy)] and its derivatives have been reported. " The Ru =0 species is an efficient DNA cleavage agent it cleaves DNA by sugar oxidation at the 1 position, which is indicated by the termini formed with and without piperidine treatment and by the production of free bases and 5-methylene-2(5//)-furanone. Kinetic studies show that the I -C— activation is rate determining and a hydride transfer mechanism is proposed. The Ru =0 species also oxidizes guanine bases via an 0x0 transfer mechanism to produce piperidine-labile cleavages. 

Julius Rebek and his group were also active at about the same time with enzyme-free self-replication of chemical structures. Unhke von Kiedrowski group, he did not use nucleotides, but a rephcator consisting of an adenosine derivative and a derivative of Kemp s acid (Rotello etal., 1991 Rebek, 1994). See also Figure 7.7 for a self-replicating system not based on nucleic-acid chemistry. There are several variations of this scheme, which are not illustrated here - for reviews see Sievers etal, 1994 Orgel, 1995. 

---