Nucleic acids polymerization

Targeting of therapeutics, whether they are chemical entities, peptides, proteins or nucleic acid polymeric substances, relies on the release of the drug from the carrier and subsequent access to the molecular target. Advances in the understanding of membrane structure, functions and properties of the various cellular organelles is the basis for directing the pharmacologically active components to the correct cellular compartments [39]. 

Differences in the sequence of homologous proteins in different species are derived from the primordial pools and are a product of the redundancy of nucleic acid polymerization and reiterations by complementary reproduction of nucleic acid strands. Sequence repeats in different proteins that could not have come about by chance (here I agree with Darwinians) do arise quite naturally from untargeted reiteration in the primordial pool. 

Another group of RNA viruses called retroviruses also contain a unique nucleic acid polymerizing enzyme called reverse transcriptase or RNA-dependent DNA polymerase, since the genetic code here is taken from RNA, which is reverse of the host cell s normal mechanism. The uniqueness in this case should also theoretically permit selective control, thereby preventing retrovirus replication.12... 

Electrochemical enzyme sensors for 140 analytes have been described. Among them are low (relative) molecular mass substances (metabolites, drugs, nutrients, gases, metal ions, coenzymes, enzyme activators, and vitamins) as well as macromolecules (enzymes, lectins, nucleic acids, polymeric carbohydrates like starch and cellulose), viruses, and microorganisms. The analytes may be roughly subdivided as follows ... 

Even though these intramolecular hydrogen bonds are relatively weak ( 5 kcal/mol) they are critically important. For example, life as we know it is clearly not possible without water and there would be no liquid water without hydrogen bonds. Moreover, hydrogen bonds are used to mainttun the proper structures in proteins and nucleic acids, polymeric structures essential to our existence that we will meet later in this book. 

Spontaneous nucleic acid polymerization is not perfect, however several obstacles needed to be overcome in evolution, likely with the aid of early enzymes. Firstly, this reaction is not particularly efficient. Nucleoside 5 -phosphorimi-dazolides are not used in nature their highly activated leaving groups make spontaneous polymerization reactions measurable on a laboratory time scale. Biology uses nucleoside 5 -triphosphates, which react more slowly. Secondly, all activated nucleotides do not react at the same rate. G, for example, is incorporated across a template C much more quickly than T or U across A [27]. Finally, spontaneous polymerization is prone to error Watson-Crick base pairing is not always conserved. 

Infubition of nucleic acids polymerization. The presence of proflavine in the reaction mixture markedly inhibits the in vitro activity of both DNA-dependent DNA and RNA polymerases (Fig. 4). The inhibition is due to the acridine binding on the DNA primer, since the degree in inhibition produced by a given drug concentration depends on the amount of DNA primer which is present in the incubation mixture. 

The macromolecules of cells are built of units—amino acids in proteins, nucleotides in nucleic acids, and carbohydrates in polysaccharides—that have structural polarity. That is, these molecules are not symmetrical, and so they can be thought of as having a head and a tail. Polymerization of these units to form macromolecules occurs by head-to-tail linear connections. Because of this, the polymer also has a head and a tail, and hence, the macromolecule has a sense or direction to its structure (Figure 1.9). 

FIGURE 1.9 (a) Amino acids build proteins by connecting the n-carboxyl C atom of one amino acid to the n-amino N atom of the next amino acid in line, (b) Polysaccharides are built by combining the C-1 of one sugar to the C-4 O of the next sugar in the polymer, (c) Nucleic acids are polymers of nucleotides linked by bonds between the 3 -OH of the ribose ring of one nucleotide to the 5 -P04 of its neighboring nucleotide. All three of these polymerization processes involve bond formations accompanied by the elimination of water (dehydration synthesis reactions). 

Most reactions of nucleic acid hydrolysis break bonds in the polynucleotide backbone. Such reactions are important because they can be used to manipulate these polymeric molecules. For example, hydrolysis of polynucleotides generates smaller fragments whose nucleotide sequence can be more easily determined. 

Highly polymeric phosphate esters (nucleic acids) present in all cells and recognized as essential constituents of chromosomes. 

As is well-known, nucleic acids consist of a polymeric chain of monotonously reiterating molecules of phosphoric acid and a sugar. In ribonucleic acid, the sugar component is represented by n-ribose, in deoxyribonucleic acid by D-2-deoxyribose. To this chain pyrimidine and purine derivatives are bound at the sugar moieties, these derivatives being conventionally, even if inaccurately, termed as pyrimidine and purine bases. The bases in question are uracil (in ribonucleic acids) or thymine (in deoxyribonucleic acids), cytosine, adenine, guanine, in some cases 5-methylcytosine and 5-hydroxymethylcyto-sine. In addition to these, a number of the so-called odd bases occurring in small amounts in some ribonucleic acid fractions have been isolated. 

Deoxypentose Nucleic Acids. Part II. Evidence for a Labile Polymeric Linkage in Deoxypentose Nucleic Acids, W. G. Overend, M. Stacey, and M. Webb,/. Chem. Soc., (1951) 2450-2452. 

Polymers are examples of organic compounds. However, the main difference between polymers and other organic compounds is the size of the polymer molecules. The molecular mass of most organic compounds is only a few hundred atomic mass units (for reference, atomic hydrogen has a mass of one atomic mass unit). The molecular masses of polymeric molecules range from thousands to millions of atomic mass units. Synthetic polymers include plastics and synthetic fibers, such as nylon and polyesters. Naturally occurring polymers include proteins, nucleic acids, polysaccharides, and rubber. The large size of a polymer molecule is attained by the repeated attachment of smaller molecules called monomers. 

Polymers are substances whose molecules are very large, formed by the combination of many small and simpler molecules usually referred to as monomers. The chemical reaction by which single and relatively small monomers react with each other to form polymers is known as polymerization (Young and Lovell 1991). Polymers may be of natural origin or, since the twentieth century, synthesized by humans. Natural polymers, usually referred to as biopolymers, are made by living organisms. Common examples of biopolymers are cellulose, a carbohydrate made only by plants (see Textbox 53) collagen, a protein made solely by animals (see Textbox 61), and the nucleic acid DNA, which is made by both plants and animals (see Textbox 64). 

Shapiro (2000) draws our attention to another type of problem the homopolymer problem in biogenesis. Many biogenesis hypotheses presuppose the spontaneous formation of polymeric organic replicators which were formed from a mixture of inorganic compounds these replicators consist of subunits of a known chemical species. Their structure involves a backbone which is bonded to information-transmitting residues. As we shall discuss in Sect. 6.7, not only RNA and DNA, but also proteins and peptide nucleic acids (PNA) have been suggested as possible information transmitters. Shapiro rightly considers that until now, not... 

Shapiro remained true to his role of critical observer at the ISSOL conference in 2002 in Mexico there he expressed the opinion that the beginnings of life did not involve polymers at all (be they nucleic acids or proteins, or their hypothetical precursors pre-nucleic acids or pre-proteins), but initially involved interactions between monomers, the polymeric biomolecules being formed in later phases of molecular evolution. In this monomer world , reactions were supported by small biocatalysts (Shapiro, 2002). 

Although many questions are still open, peptide nucleic acids are easier to synthesize via simple reaction routes than is natural RNA. The PNAs have another important advantage they are achiral and uncharged, i.e., they contain no chiral centres in the polymeric backbone (see Sect. 9.4). Unfortunately, however, they do not fulfil all the necessary conditions for molecular information storage and transfer. Thus, the search for other possible candidates for a pre-RNA world continues. 

In this respect, an interesting approach to reduce degradation and possible toxicity problems related to nucleic acid use in vivo is offered by their encapsulation in or association to microcarrier systems, such as neutral or cationic liposome and polymeric microparticles [41 14],... 

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