Nucleic acid analogs water-soluble

SYHTHESIS AND INTERACTI( I OF WATER SOLUBLE NUCLEIC ACID ANALOGS... 

Water soluble nucleic acid analogs were prepared by grafting uracil, thymine, 5-fluorouracil, hypoxanthine, cytosine, and adenine derivatives containing a hydroxy group onto linear poly(ethyleneimine). These polymers contained about 90 unit% of the nucleic acid bases, and were easily soluble in water at neutral pH resign. The analogs were found to form complementary polymer complexes with each other and with polynucleotides. The interaction study was made on these polymers, and with polynucleotides poly(uridylic acid) poly(U), poly(adenylic acid) poly(A), poly(inosinic acid) poly(I) and poly(cytidylic acid) poly(C) in water. They were found to form polymer complexes with polynucleotide by specific base-base interaction in aqueous solution. 

In the present study, water soluble poly(ethyleneimine) derivatives containing uracil, thymine, 5-fluorouracil, hypoxanthine, cytosine, and adenine were prepared and their interactions with polynucleotides, such as poly(A), poly(U), poly(C), poly(I) in natural aqueous solution were investigated. As 5-fluorouracil is known as a famous anticancer agent, it seems to be interest to study the interaction of the polymer containing 5-fluorouracil unit with polynucleotides. The bioactivity of the polymer complex of nucleic acid analogs with polynucleotides will be reported... 

Natural and synthetic polynucleotides are known to form polymer complexes by specific base-base interactions between nucleic acid bases. The synthetic nucleic acid analogs such as poly (methacryamide), poly-(ethyleneimine) and poly(L-lysine) derivatives containing nucleic acid bases were also found to form polymer complexes with polynucleotides by specific base-base interactions. Since the solubilities of these nucleic acid analogs in water were low, the specific interactions should be studied in organic solvents or water-organic mixed solvents, such as dimethyl sulfoxide, ethylene glucol, and water-propylene glycol. 

On the other hand, complex formation of polynucleotides and its application to biomedical field have been studied in aqueous solution, because organic solvent causes denaturation of polynucleotides. Therefore, it is necessary to prepare a water soluble polymer complex of nucleic acid analogs with polynucleotides for the biomedical uses. The water soluble poly(ethyleneimine) derivatives of nucleic acid bases open a way to study the interaction with polynucleotides in neutral aqueous solution. 

Yet another type of polyamide nucleic acids analogs with a poly-L-lysine backbone (Fig. 20c, w = 4, z = 3) was described by Takemoto et al. (37). The ribose units in this analog mainly served the purpose of enhancing solubility of the polymers in water by the free hydroxy groups. For their preparation, 2 3 -0-isopropylidene-5 -0-glutaric acid succinimido nucleosides were coupled to prepolymerized L-lysine, a procedure not allowing sequence-specific introduction of nucleobases. 

Most of the nucleic acid model compound prepared so far are water insoluble however, when the analogs are water soluble, they may not permeate into the hydrophobic cell membranes. Recently, an improved drug delivery system for water soluble drugs using polysaccharide-coated liposomes [68] was developed. 

TSKgel PW series columns have been used in the separation of water-soluble synthetic polymers, poly- and oligo-saccharides, and proteins [ref. 34-41]. Recently it has been shown that the columns can be used for lipoproteins and nucleic acids. TSKgel PW columns are available from Toyo Soda, and in other countries, from the dealers listed in Table 3. Showa Denko developed an analogous type of columns, namely OHpak B-800 [ref. 42, 43]. Properties of these columns are represented in Table 4. 

Relatively little work has been done on the biological effects of water soluble polymers (14-16). The polyvinyl analogs of nucleic acids described here and in previous reviews (1,17) together with... 

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