Globular nucleic acids

The neutral hydrophilic surface and the wide range of pore diameters available for SynChropak GPC allow many compounds from small peptides to nucleic acids and other polymers to be analyzed. Table 10.2 lists the approximate exclusion limits for both linear and globular solutes. Although this information... 

Linding, R., Russell, R. B., Neduva, V., and Gibson, T. J. (2003). GlobPlot Exploring protein sequences for globularity and disorder. Nucleic Acids Res. 31, 3701-3708. 

Both the denaturation process in proteins and the melting transition (also referred to as the helix-to-coil transition) in nucleic acids have been modeled as a two-state transition, often referred to as the all-or-none or cooperative model. That is, the protein exists either in a completely folded or completely unfolded state, and the nucleic acid exists either as a fully ordered duplex or a fully dissociated monoplex. In both systems, the conformational flexibility, particularly in the high-temperature form, is great, so that numerous microstates associated with different conformers of the biopolymer are expected. However, the distinctions between the microstates are ignored and only the macrostates described earlier are considered. For small globular proteins and for some nucleic acid dissociation processes,11 the equilibrium between the two states can be represented as... 

Katsura, S., Hirano, K., Matsuzawa, Y., Yoshikawa, K. and Mizuno, A. (1998) Direct laser trapping of single DNA molecules in the globular state. Nucleic Acids Res., 26, 4943M945. 

While this notion may conjure up visions of plastic materials it is important to remember that proteins and nucleic acids are also polymers. Many proteins form globular structures and, indeed, may interlock to encapsulate a large volume of space as exemplified by the coatings of capsid viruses. In a prebiotic world, polypeptides could have formed in aqueous solution through the sequential reaction of amino acids. The individual amino acids hydrogen bond donor and acceptor groups, amines, carbonyls and carboxylic acids, would all have helped to keep the molecules in solution. Once a polypeptide had formed, however, many of these would be unavailable as they became incorporated in the hydrogen bond network that formed the secondary and tertiary structure. This would result in a more hydrophobic surface for the protein capsule which would make an effective cell. 

The life that we know also uses proteins for the majority of structural and catalytic functions. Proteins are particularly suited for these functions because of the structural properties of polymers of amino acids. The polyamide backbone of proteins is neutral, unlike that of nucleic acids. Further, the backbone has a repeating dipole able to make hydrogen bonds. These structural features are exploited as proteins fold into globular structures, as they promote the formation of stable secondary structures such as alpha helices and beta sheets. 

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. 

This behavior can be seen as complementary to another aspect of protein folding the withdrawal of hydrophobic side chains from solvent. The latter minimizes perturbation by burying those portions of the polypeptide for which water is the poorest solvent. The former minimizes perturbation of solvent by what remains exposed. Not all biological macromolecules show so small an effect. Nucleic acids require for their hydration about twice the amount of water required by globular proteins (for heat capacity measurements comparing protein and tRNA, see Rupley and Siemankowski, 1986). It may be signihcant that DNA, with an extensive hydration shell, undergoes facile hydration-dependent conformational transitions, which are not found for proteins. 

The major analytes in this category are the alicyclic compounds (alkaloids and terpenes) heterocyclic compounds (barbiturates, benzodiazapams, indole alkaloids, quinolines, nucleic acids, and nucleotides) aminoacids and peptides oligopeptides and proteins (globular, nucleo-, and lipo-) saccharides and polysaccharides and condensation products of saccharides with all the other analytes, e.g., glucuronides and gly-coproteins. Thus far, most analyses have been done on solid and solution forms of the drug substances. A few illustrations are reported in which CD was used in the direct analysis of biological extracts. 

AChE and BuChE subunits are synthesized within cells (e.g., nerve, muscle, liver, and some megakaryocytes), glycosylated within the Golgi apparatus, and secreted. Collagen-tailed forms become attached to the cell surface at specific binding sites. Globular forms are released into body fluids or bind to cell surfaces by ionic bonds. Antibodies have been prepared to several purified AChEs and BuChEs, and protein and nucleic acid sequences have been determined. 

A characteristic of multiple sclerosis, denaturation The structural and functional changes to globular protein or nucleic acid in solution, brought about by extremes of heat, pH, some chemicals or X-rays, dendrite A short branching process of the neuronal cell body which synapses with other neurons, dendrite celis Mobile, non-phagocytic cells derived from bone marrow and which come specialized for particular functions. 

George, R. A., K. Lin, and J. Heringa. 2005. Scooby-domain prediction of globular domains in protein sequence. Nucleic Acids Res 33 W160-3. 

Although X-ray diffraction methods have proved to be extremely successful in the determination of a wide variety of biomolecular structures, including both globular and fibrous proteins and nucleic acids, polysaccharides and macromolecular assem-... 

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