Noriyuki Miyauchi

Potent Immunomodulating Activities of Polyvinyladenine and (Vinyladenine-Alt-Maleic Acid) Copolymer

Polyvinyladenine [poly(VAd)] and poly(vinyladenine-alt,co-maleic anhydride) [poly(VAd-MA)] were prepared by free radical polymerization of vinyladenine and copolymerization of vinyladenine with maleic anhydride.

High-performance affinity chromatography of oligonucleotide on nucleic acid analogue immobilized silica gel columns

The nucleic acid analogues poly(9-vinyladenine) (PVAd), poly(9-adenylethyl methacrylate) and poly(thymylethyl methacrylate) (PTM) were chemically bonded to porous silica gel, which had been pretreated with 3-trimethoxysilylpropyl methacrylate, by free radical copolymerization to produce novel packing materials for affinity chromatographic columns. The columns separated nucleosides and nucleotide dimers on the basis of hydrophobic interaction using an aqueous buffer and complementary hydrogen bonding interaction in methanol as an eluent. The PVAd- and PTM-silica gel columns gave a nucleobase-selective separation of oligonucleotides differing in length from mixtures of oligoadenylic and oligouridylic acids. On the PVAd-silica gel column terminal phosphate isomers of oligouridylic acid up to seven mer were resolved and the elution order of the isomers was different from that on an ODS column.

Review : Polymer Drugs and Polymeric Drugs: Part 3-Synthesis and Hydrolysis of Acryloyl and Methacryloyl Type Polymeric Drugs Containing 5-Fluorouracil and Theophylline

Acryloyl and methacryloyl derivatives of 5-fluorouracil and theophylline were synthesized by the reaction of trimethylsilylated 5-fluorouracil or theophylline with acryloyl chloride or methacryloyl chloride. Polymerization and copoly merization of derivatives with vinyl monomers gave polymeric drugs contain ing pharmaceutically active 5-fluorouracil or theophylline. Under mild conditions, these acryloyl and methacryloyl type polymeric drugs were found to undergo amide hydrolysis to release the 5-fluorouracil or theophylline.

Antithrombogenic Poly(vinyl chloride) with Heparin- and/or Prostaglandin I2-Immobilized in Hydrogels:

Poly(vinyl chloride) (PVC) with heparin- and/or prostaglandin I2 (PGI2)- immobilized on crosslinked polyacrylamide hydrogels were prepared by the ad dition of the dry hydrogels to a PVC tetrahydrofuran solution. Immobilized heparin was found to be continuously released from the PVC matrix at 37 ° C in a physiological saline. Antithrombogenic activity of PVCs with heparin and/or PGI2 was evaluated by activated partial thromboplastin time (aPTT), whole blood clotting time, and inhibition of platelet aggregation. The heparin- immobilized PVCs exhibited excellent anticoagulant activity and the PGI2 immobilized PVCs completely inhibit platelet aggregation of human blood after sitting for 46 h in a physiological saline.

Synthesis and Properties of Hydrophilic Copolymers Containing 5-Fluorouracil, Thymine, or Adenine

Abstract Hydrophilic copolymers containing 5-fluorouracil (5-FU), thymine, or adenine were prepared by the free-radical copolymerization of methacryloyl-type monomers containing them with water-soluble vinyl monomers such as acrylic acid, methacrylic acid, vinylpyrroli-done, acrylamide, and 4(5)-vinylimidazole with AIBN as initiator. Complex formation between the copolymers and RNA and between the copolymers having complementary nucleic acid bases in aqueous solution and a DMSO-ethylene glycol was studied by means of UV spectroscopy. These copolymers were found to release the N-hydroxyethyl derivatives of 5-FU, thymine, or adenine by hydrolysis of the ester of the polymer side chain under mild conditions. The effects of the kind of water-soluble comonomer, temperature, pH, and the imidazole group as catalyst on the hydrolysis of the ester are discussed.

Affinity gel electrophoresis of nucleic acids. Specific base- and shape-selective separation of DNA and RNA on polyacrylamide-nucleobase conjugated gel.

Two types of affinity gels consisting of cross-linked polyacrylamide and affinity ligands possessing nucleic acid bases were prepared. One type of gel was polyacrylamide-poly(vinylnucleobase) conjugated gel, where the poly(vinylnucleobase) such as poly(9-vinyladenine) (PVAd) bearing a nucleobase in the side-chain was entrapped in the gel matrix. The other type of gel, in which a nucleobase such as adenine is chemically bonded to polyacrylamide gel, was prepared by copolymerization of acrylamide, cross-linker and 9-vinyladenine. These affinity gels, especially the former, demonstrated characteristic nucleobase- and shape-selective separation of nucleic acids. The gels showed high affinity for single-stranded DNA and both single- and double-stranded polynucleotides and could separate a double-stranded DNA in mixtures of double-stranded DNA and polynucleotides. The electrophoretic mobilities of poly(uridylic acid) and poly(inosinic acid) were selectively retarded even in the presence of 7 M urea. The electrophoretic behaviours of nucleic acids on the polyacrylamide-PVAd conjugated gels were compared with those on the agarose-PVAd conjugated gel. The effects of urea, temperature and concentration of PVAd were also examined. The polyacrylamide-PVAd conjugated gel served to elucidate interactions between PVAd and nucleic acids that could not be detected by usual spectroscopic methods.

Affinity gel electrophoresis of nucleic acids: Nucleobase-selective separation of DNA and RNA on agarose-poly(9-vinyladenine) conjugated gel

Poly(9-vinyladenine) (PVAd) was immobilized within an agarose gel matrix to produce a novel affinity gel for the base-specific separation of nucleic acids by electrophoresis. The shape (single- or double-stranded) and base content of nucleic acids were specifically recognized by the affinity gel. Only single stranded DNA, of which the sequence is not regular enough to form a stable duplex hairpin structure, was selectively absorbed over double-stranded DNA. Among five polynucleotides having different bases such as poly(A), poly(G), poly(C), poly(U) and poly(I), poly(U) and poly(I) were base-specifically adsorbed by PVAd, probably by hydrogen bond formation. The effect of the molecular mass and size of poly(9-vinyladenine) was also examined.

Polymer Drugs and Polymeric Drugs, Part VII*: Antitumor Conjugated Polymeric Drugs Consisting of 5-Fluorouracil and Polyanionic Polymers

Derivatives of 5-flurorouracil 1-N-p-vinylbenzoyl-5-fluorouracil (VBFU) were prepared and the solvolysis rates were determined and compared with other 1-N-substituted 5-fluorouracils. VBFU was homopolymerized and copolymerized with maleic anhydride or poly(ethylene glycol) macromonomer. The hydrolysis of these polymeric drugs was studied in a phosphate buffer solu tion, and in vivo antitumor activity was evaluated using Ehrlichs ascites or Sarcoma 180 tumor-bearing mice.

Hardening of Butylated Melamine Coating Resins

ブチル化メラミン樹脂の熱硬化反応機構を検討する目的で,組成を異にする3種の樹脂を調製してそのブタノール溶液(60%)をガラス板上に塗布し加熱硬化させた。硬化樹脂を分析してその組成より各官能基の変化を求め,また生成樹脂の赤外吸収スペクトルを測定して,この両者の結果と加熱減量曲線から硬化反応についてつぎの知見を得た。1.ブチル化メラミン樹脂は塗料として用いる通常の焼付け温度(120～150℃)においても,脱ブタノール反応が脱ホルムアルデヒド反応とともに明らかに認められた。2.この脱ブタノール反応は120℃においてはiおよびiiが同時に起こり,150℃においてはiiiも若干加わることもあると推定される。

etallic Resins. I. Aluminum Alcoholate Resin Coatings

アルミニウムを含有する合成樹脂初期縮合物溶液を合成して塗料に使用する目的で,まず塩化アルミニウムを過剰のエチレングリコール・グリセリンと直接無触媒およびジアミン触媒存在下に縮合させ,水酸基を多量に有する縮合物を合成して,この水酸基を乾性油脂肪酸でエステル化し,アルミニウムアルコラート樹脂溶液を得た。しかし,このものの塗料としての性質は不満足であったので,つぎにアルミユウムイソプロポキシドのモノキレートをつくり,これを当量のペンタエリトリットジ乾性油脂肪酸エステルと反応させて,残存する2個のイソプロポキシル基をペンタエリトリットエステルの残存水酸基によりアルコラート交換反応を起させて,同じく乾性油脂肪酸基を持つアルミニウムアルコラート樹脂溶液を得た。これは常温で極めて速乾性のワニスとして用いられ,かつその塗膜はすぐれた硬度その他の性質を有することを知った。