Nucleic acids building blocks

Nucleic acids are composed of nucleotide monomers, which themselves are built from a phosphate group, a sugar, and a nitrogenous base. The bases are of two types, pyrimidines (single ringed) and purines (double ringed). 

Nucleosides and nucleotides are combinations of a base with a sugar. A nucleoside is an N-glycoside formed between a base and a sugar (usually ribose or deoxyribose). A nucleotide is a phosphate ester of a nucleoside. DNA nucleotides are more stable to acid hydrolysis of the glycosidic bond, which is one reason tfrat DNA has superceded RNA as the main genetic storage molecule it is less prone to mutation. 

Base Ribonucleoside (Base + Ribose) Ribonucleotide (Base + Ribose + Phos.) 

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Leslie Orgel and co-workers took up this problem and studied the non-enzymatic polymerisation of mononucleotides, i.e., the question as to whether single nucleic acid building blocks can undergo polycondensation on a corresponding complementary matrix. The substrates used were the 5 -phosphoimidazolides of adenosine (ImpA) and guanosine (ImpG), the matrices poly(U) and poly(C). 

This review is focused on hi er-order base motifs where more than two bases are linked by H-bonds. We call these nucleic acid building blocks base triads, tetrads, pentads,. .. and in general base polyads. Alternative names for these base motifs are triple, quartet, quintet,. Multistranded structure that... 

DNA can be affected by chemical and environmental effects. D. M. Close presents a review of primary radiation-induced defects in nucleic acid building blocks. The discussion includes both EPR/ENDOR experiments and the application of quantum chemical calculations of spin densities and isotropic and anisotropic hyperfine couplings that could be used to assist in making fi ee radical assignments. DFT theory has been selected for theoretical predictions. The chapter presents examples of successes and failures of the DFT calculations in the prediction of spin densities and hyperfine couplings for radiation-induced radicals observed in nucleobases. In addition, a discussion of unsolved problems and suggestions for future directions is also given. 

Templates are synonymous with the proliferation of life in biological systems. There is no need here to detail the way that DNA and RNA work to template their own formation. Suffice to say that they are the paradigm of a linear template, whereby not only the length of the replicated strand is determined by the template strand but also the sequence of the nucleic bases is strictly reproduced. This naturally occurring system is also exploitable for the preparation of entirely synthetic systems of varying complexity using the same nucleic acid building blocks, which are reviewed elsewhere in this volume (see Self-Assembly of Nucleic Acids, Self-Processes). 

Complete hydrolysis of nucleic acids (see Section 3.4) by chemical or enzymatic means liberates the nucleic acid building blocks" phosphate, sugar (ribose or deoxyribose), and bases, in a 1 1 1 ratio. Depending on the conditions of the hydrolysis, larger compounds containing these building blocks are obtained (oligonucleotides). 

Substances such as these may interfere with nucleic acid replication by masquerading as legitimate nucleic acid building blocks. The enzymes associated with this process are fooled into incorporating the drug molecule, and the synthesis of the biological polymer cannot continue. For example, the base thymine is derived biosyntheticaUy by... 

Nucleotides ate the basic nucleic acid building blocks. Thus, the study of their dynamics, hydration patterns, as well as those of their constituent fragments, i.e., phosphates, sugars, and bases, gives interesting insights in the structure of bigger... 

Transfer RNA (tRNA) molecules mediate translation of the nucleic acid genetic code into the amino acid building blocks of proteins, thus ensuring the survivability of cells. The dynamic properties of tRNA molecules are crucial to their functions in both activity and specificity. This chapter summarizes two methods that have been recently developed or improved upon previous protocols to introduce fluorophores to site-specific positions in tRNA. One method enables incorporation of fluorophores carrying a primary amine (such as proflavin or rhodamine) to dihydrouridine (D) residues in the tRNA tertiary core, and a second method enables incorporation of pyrroloC and 2-aminopurine to positions 75 and 76, respectively, of the CCA sequence at the 3 end. These site-specific fluorophore labeling methods utilize tRNA transcripts as the... 

A short introduction to peptide synthesis will be given before the synthesis of glycopeptides is discussed. Proteins are assembled by a nucleic acid templated reaction from a menu comprising 19 L-oc-amino acids of general structure 1 and the amino acid L-proline (2) (Figure 5.1). Nature synthesises proteins by a stepwise assembly of amino acid building blocks. Since these compounds are readily available in... 

We have come a long way in the journey toward understanding the molecular basis of life. Half a century ago, Francis Crick proposed the central dogma as a working model that credits the three-dimensional structure and function of proteins to their one-dimensional progenitors DNAs and RNAs [38], However, the discovery of posttranslational modification (PTM) makes it clear that the structure and function of proteins and polypeptides can be dictated by factors other than their encoding nucleic acids and amino acid building blocks [39]. 

The most important derivatives of pyrimidines and purines are nucleosides Nucleosides are N glycosides m which a pyrimidine or purine nitrogen is bonded to the anomeric carbon of a carbohydrate The nucleosides listed m Table 28 2 are the mam building blocks of nucleic acids In RNA the carbohydrate component is d ribofuranose m DNA It IS 2 deoxy d ribofuranose... 

Any one nucleotide, the basic building block of a nucleic acid, is derived from a molecule of phosphoric acid, a molecule of a sugar (either deoxyribose or ribose), and a molecule of one of five nitrogen compounds (bases) cytosine (C), thymine (T), adenine (A), guanine (G), uracil (U). 

Cellular Protein Biosynthesis. The process of cellular protein biosynthesis is virtually the same in all organisms. The information which defines the amino acid sequence of a protein is encoded by its corresponding sequence of DNA (the gene). The DNA is composed of two strands of polynucleotides, each comprising some arrangement (sequence) of the four nucleotide building blocks of the nucleic acids adenine (A), thymine (T),... 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

Epoxides are often encountered in nature, both as intermediates in key biosynthetic pathways and as secondary metabolites. The selective epoxidation of squa-lene, resulting in 2,3-squalene oxide, for example, is the prelude to the remarkable olefin oligomerization cascade that creates the steroid nucleus [7]. Tetrahydrodiols, the ultimate products of metabolism of polycyclic aromatic hydrocarbons, bind to the nucleic acids of mammalian cells and are implicated in carcinogenesis [8], In organic synthesis, epoxides are invaluable building blocks for introduction of diverse functionality into the hydrocarbon backbone in a 1,2-fashion. It is therefore not surprising that chemistry of epoxides has received much attention [9]. 

Streptavidin-single-stranded DNA covalent conjugates were described as the building blocks for assembling nanostructured scaffolds [31], The amount and type of biotinylated ligands were used to modulate the affinity of duplex formation between solid-phase-bound nucleic acid templates and DNA-streptavidin conjugates. This system has been proposed for the design of fine-tuned sequence detection systems. 

The kinetics of feedback inhibition may be competitive, noncompetitive, pattially competitive, ot mixed. Feedback inhibitots, which frequently ate the small molecule building blocks of mactomolecules (eg, amino acids for proteins, nucleotides fot nucleic acids), typically inhibit the fitst committed step in a particulat biosynthetic sequence. A much-studied example is inhibition of bacterial aspattate ttanscatbamoylase by CTP (see below and Chaptet 34). 

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