Polynucleotide analogs

Interactionof Polynucleotide Analogs with Cells in Culture. 10... 

Further in this review we will deal with fully synthetic analop of polynucleotides, (compare examples in Fig. 2.), that do not have stereoregular structures. Thus, the first important aspect of similarity to nucleic acids is lost. The ateence of stereoregularity renders polynucleotide analogs ineffective in biological syntheses where natural polynuc-... 

Fig. 2. Structures of backbones of polynucleotide analogs and natural polynucleotides. If base in question is adenine, then the compounds are 1) poly-9-vinyl-adenine, 2) copolymer of 9-vinyladenine and maleic acid, and 3) polydeoxyadeiqrlate...

Electric charge has crucial importance to the bioeffects of polynucleotide analogs and can be used to subdivide these compounds into three subgroups (i.e., electroneutral, polyanions, polycations) that have distinctly different biochemical effects. 

Polynucleotide analogs that are polyanions (Fig. 2) have again a number of properties in common. The association of polyanionic analogs with natural polynucleotides is rather weak or, in some cases, even non existent. This is due to a combination of the presence of electronegative diarges and the lack of stereoregularity. Thus, whereas there are as many coulombic repulsions in effect as in cranplexes of nucleic acids, only a few base pairs, which hold different strands tc ether, can be formed. On the other hand, the presence of... 

From various physical and biophysical properties of nucleic acid analogs the most important property for the present purpose is their interaction with nucleic acids. The spectrophotometric methods for detection of complex formation were applied to all combinations of polyvinyl polynucleotide analogs and natural polynucleotides (Fig. 3). In aqueous media hypochromic complexes were formed in combinations where the bases in the polynucleotide and analog were complementary. Poly-l-vinylcytosine is soluble in aqueous-propylene glycol base-pair type complexes were detected there also. An analog of polyinosinate, poly-9-vinylhypoxanthine, is soluble only in solutions of a detergent, sodium dodecylsulfate. This detergent intercalates into the polymer and conveys to it an... 

Fig. 3. Formation of complexes between various combinations of polynucleotide analogs and natural polynucleotides. Abbreviations used poly VA, poly-9-vinyladenine poly VU, poly-l-vinjl-uradl y VC, poly-l-vinylcytosine poly VHX, poly-9-vinylhypoxanthine SDS, sodium dodecyl sulfote...

There are two possible mechanisms by which a polynucleotide analog can inhibit the polymerase in the template-specific manner. Polynucleotide analogs can displace polymerase from its template and release the enzyme into solution in a free form alternatively, the polymerase can become blocked on the template polynucleotide analog complex and remain there in a bound, inactive form. These alternatives were investigated for two enzymes, alpha class DNA polymerase and E. colt RNA polymerase. In both cases the polymerase becomes blocked on the polynucleotide templates rather than being released in free form ... 

Specific inhibition of templated biosynthesis by electroneutral polynucleotide analogs can be achieved even with complex templates Messenger RNA coding for globin, similarly to other messenger RNA molecules, contains a polyadenylate sequence located... 

Polynucleotide Analogs and Cells in Culture 4.1. Cells in Culture... 

The presently known polynucleotide analog cannot penetrate the cytoplasmic membrane and probably are unable to interact with the receptors and transport systems located there consequently, only nonspedfic interactions take place upon exposure of cells to polynudeotide analogs. 

The surface of cells is constantly renewed the new plasma membraiK is synthraized in the cell and translocated to the surface while parts of the existing membrane are internalized in the endocytotic process, illustrated in Fig. 4. During the endocytotic process the polymer that was adsorbed on the cell surface and a small portion of the polymer in the surrounding medium enter into cells these polymers are enclosed in endocytotic vesicles. The internalized polymers stay firmly assodated with the cells. When the internalized poly-9-vinyladenine was followed for three cell divisions, the amount correlated with the number of viable cells within experimental error. Thus,no degradation or excretion of polynucleotide analogs from cells occurred. The cells containing radioactive polymer were also fractionated and (fistribution of radioactivity in aU these fractions was measured. Results confirm that a substantial amount of the polymer was in an enveloped form, probably in endocytotic vesides and lyM)somes ... 

Fig-2. Structures of backbones of polynucleotide analogs and natural polynucleotides. If base in question is... 

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