Nucleic Acid Derivatives of Polysaccharides

The principles of attachment of molecules to polysaccharides with concomitant insolubilization, discussed in the preceding two Sections, also apply to nucleic acids. The insolubilization of nucleic acids and polynucleotides provides materials useful (a) for fractionation and purification of other nucleic acids and related compounds,(b) for multiplication and isolation of single nucleic acid strands by base-pairing, (c) for base-sequence determination, (d) as afiR-nants, templates, and substrates for nucleic acid-related enzymes, and (e) as aflBnants for nucleic acid-binding proteins.  

Covalent coupling to the insoluble matrix is preferable, as before, and also permits the position of attachment in, and orientation of, the polynucleotide chains to be known. As the terminal nucleotides both of synthetic and natural polynucleotides possess structures different from those forming the internal parts of the chain, it is possible to utilize such terminal groups selectively in doing so, overcrowding is avoided, and maximum accessibility is achieved. 

Polysaccharides, particularly cellulose, have been used almost exclusively in the insolubilization of nucleic acids. The principal, covalent, nucleic acid derivatives of polysaccharides are shown in Table V. Syn- 

Insoluble derivatives of antibiotic substances hold potential for (a) the formation of bactericidal and fungicidal surfaces, (b) chromatographic columns and functional membranes protected from microbial attack, and (c) slow-release forms of antibiotics. They could have numerous applications in medicine, industry, and the laboratory. 

Little work has, however, been done on the preparation of insolubilized antibiotics, but, in view of the success of initial trials, the field may be expected to develop quite rapidly. Many of the polysaccharide derivatives discussed in the present article may have antibiotic characteristics, although few have been tested for such. Furthermore, many of the polysaccharide derivatives used for insolubilization of other molecules (see Sections VIII-X, pp. 361-387) are suitable for insolubilization of antibiotics, the choice of derivative depending upon the functional groups available in the particular antibiotic substance under consideration. 

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There is increasing interest in the development of foldamers or polymeric structures that can adopt organised secondary structures like those of proteins, nucleic acids and some polysaccharides [42]. Sugar amino acid-based foldamer research has so far been primarily concerned with synthesis of polymers with secondary sfructural features. Such foldamers may find application as scaffolds for peptidomimetic development if they adopt turn, helical and strand sfructures observed for peptides or if derivatives can act as ligands for peptide receptors ... 

An important group of enzymatically derived polymers is polyesters. In nature, they hold the fourth place after the three major biomacromolecules (nucleic acids, proteins, and polysaccharides). Important polyesters are poly(ethylene terephthalate) (PET), poly(butylene succinate) (PBS), poly(e-caprolactone) (poly(e-CL)), and poly(lactic acid) (PLA) (see Fig. 3.40). The former two are industrially produced via polycondensation and the latter two via ROP. Additionally, enzymes can be used to hydrolyze ester bonds, which offers the possibility to recycle commercially used materials, for example, PET [52]. 

An enormous amount of articles and reviews have been published during the last fifteen years supports are of very different types, with poly(vinyl alcohol) or polysaccharides being chosen each time hydrophobic properties are desired. Polyethyleneimine is used as a vehicle for nucleoside residue and nucleic acid derivatives. " ... 

Cell components or metabolites capable of recognizing individual and specific molecules can be used as the sensory elements in molecular sensors [11]. The sensors may be enzymes, sequences of nucleic acids (RNA or DNA), antibodies, polysaccharides, or other reporter molecules. Antibodies, specific for a microorganism used in the biotreatment, can be coupled to fluorochromes to increase sensitivity of detection. Such antibodies are useful in monitoring the fate of bacteria released into the environment for the treatment of a polluted site. Fluorescent or enzyme-linked immunoassays have been derived and can be used for a variety of contaminants, including pesticides and chlorinated polycyclic hydrocarbons. Enzymes specific for pollutants and attached to matrices detecting interactions between enzyme and pollutant are used in online biosensors of water and gas biotreatment [20,21]. 

This subject has been of continuing interest for several reasons. First, the present concepts of the chemical constitution of such important biopolymers as cellulose, amylose, and chitin can be confirmed by their adequate chemical synthesis. Second, synthetic polysaccharides of defined structure can be used to study the action pattern of enzymes, the induction and reaction of antibodies, and the effect of structure on biological activity in the interaction of proteins, nucleic acids, and lipides with polyhydroxylic macromolecules. Third, it is anticipated that synthetic polysaccharides of known structure and molecular size will provide ideal systems for the correlation of chemical and physical properties with chemical constitution and macromolecular conformation. Finally, synthetic polysaccharides and their derivatives should furnish a large variety of potentially useful materials whose properties can be widely varied these substances may find new applications in biology, medicine, and industry. 

Microbial mats and biofilms, defined as surface layers of microbes entrained in a matrix of extracellular polymeric substances (EPS) (Characklis and Marshall, 1989), are also important in changing the surface texture and erodibility of sediments in estuaries (de Beer and Kiihl, 2001). The EPS are primarily composed of cellular-derived polysaccharides, polyuronic acids, proteins, nucleic acids, and lipids (Decho and Lopez, 1993 Schmidt and Ahring, 1994). The EPS can serve as a cementing agent for surface sediment particles, thereby affecting the erodibility of sediments as well as the flux of dissolved constituents across the sediment-water interface (de Beer and Kiihl, 2001). 

Several pharmaceutical activities of nucleic acid analogs such as poly(VAd) have been studied in vitro and in cell-free systems [19]. It was expected that the present polymers would be effectively transferred into phagocytes by encapsulating in polysaccharide-coated liposomes and would show increased pharmaceutical activities similar to poly(maleic acid-a/l-2-cyclohexyl-l, 3-dioxap-5-ene) (MA-CDA) [68]. The activation of human neutrophils by poly(VAd) was evaluated by monitoring the in vitro superoxide anion production from activated human neutrophils. Shown in Table 15 is the superoxide liberated from human neutrophils (1 x 106 cells/ml) activated by poly(VAd) (0.5 mg/ml) as a function of time. Poly(VAd) encapsulated in mannan derivative-coated liposomes showed a... 

Of the three major components of biological structure, the proteins, nucleic acids, and polysaccharides, least is known about the polysaccharides at the secondary and tertiary level of molecular structure. This is because the polysaccharides cannot be obtained in crystals which are large enough for single crystal X-ray or neutron structure analysis. What structural information there is comes from fiber X-ray diffraction patterns. However good these diffraction patterns are, the structures derived from them will always be model-dependent. This is because the number of variable atomic parameters which determine the diffraction intensities exceeds the number of observed intensities. 

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