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N Kakiuchi

Publications and source records attributed to N Kakiuchi.

48 records · Page 3Linked to original sources
PubMed1979

Influence of various 2- and 2'-substituted polyadenylic acids on murine leukemia virus reverse transcriptase.

Several newly synthesized polyadenylic acid [(A)n] analogues, including poly(2-methyladenylic acid) [(m2A)n], poly(2-ethyladenylic acid) [(e2A)n], poly(2-isopropyladenylic acid) [(i-pro2A)n], poly(2-methylthioadenylic acid) [(ms2A)n], poly(2-ethylthioadenylic acid) [(e2A)n], poly(2'-fluoro-2'-deoxyadenylic acid) [(dAfl)n] and poly(2'-azido-2'-deoxyadenylic acid) [(dAz)n] have been evaluated for their effects on the RNA-directed DNA polymerase (reverse transcriptase) activity of Moloney murine leukemia virus; (m2A)n and (e2A)n did not markedly affect reverse transcriptase activity, (dAfl)n served as an efficient template for the reverse transcriptase reaction, and (i-pro2A)n, (ms2A)n, (es2A)n and (dAz)n strongly inhibited reverse transcriptase activity. (dAfl)n also served as an efficient template (Km : 0.025 micron) for the reverse transcriptase of avian myeloblastosis virus.

Avian Myeloblastosis Virus↗
PubMed1978

Polynucleotides. XLIV. Synthesis and properties of poly (2-azaadenylic acid) and poly(2-azainosinic acid).

Chemically synthesized 2-azaadenosine 5'-diphosphate (n2ADP) and 2-azainosine 5'-diphosphate (n2IDP) were polymerized to yield poly(2-azaadenylic acid), poly(n2A), and poly(2-azainosinic acid), poly(n2I), using Escherichia coli polynucleotide phosphorylase. In neutral solution, poly(n2A) and poly(n2I) had hypochromicities of 32 and 5.5%, respectively. Poly(n2A) formed an ordered structure, which had a melting temperature (Rm) of 20 degrees C at 0.15 M salt concentration. Upon mixing with poly(U), poly(n2A) formed a 1 : 2 complex with Tm of 41 degrees C at 0.15 M salt concentration. Poly(n2A) and poly(n2I) formed three-stranded complexes with poly(I), and poly(A), respectively. Poly(n2A) . 2poly(I), poly(A) . 2poly(n2I), and poly(n2A) . 2poly(n2I) complexes had Tm values of 23, 48, and 31 degrees C at 0.15 M salt concentration, respectively. Poly(n2I) formed a double-stranded complex with poly(C), but its Tm was very low.

Circular Dichroism↗
PubMed1978

Polynucleotides. LII. Synthesis and properties of poly(2'-deoxy-2'-fluoroadenylic acid).

2'-Deoxy-2'-fluoroadenosine was chemically transformed to its 5'-diphosphate and polymerized with polynucleotide phosphorylase to give poly(2'-deoxy-2'-fluoroadenylic acid) [poly(Af)]. Polymerization proceeded smoothly as in the case of poly(A) and the yield of the polymerization was 55%. The UV absorption spectra of poly(Af) closely resembled those of poly(A) and the hypochromicity was 32% at pH 7.0. The CD profile at 25 degrees and neutrality showed similar pattern to that of other poly(2'-deoxy-2'-halogenoadenylic acids) with somewhat larger [theta] values both in the positive and negative maxima. Acid titration of poly(Af) showed a transition point at pH 5.2 and the Tm of the acid form was 37 degrees which was significantly lower than that of poly(A), but similar to that of poly(2'-azido-2'-deoxyadenylic acid). Poly(Af) formed 1:1 and 1:2 complexes with poly-(U) having Tm of 49 degrees and 62 degrees at 0.04M and 0.15M Na(+) concentration, respectively. Poly(Af) also formed a 1:2 complex with poly(I) and its Tm was 36 degrees at 0.05M Na(+) concentration. These data showed that poly(Af) has rather similar properties to those of poly(A), but not to poly(dA).

Circular Dichroism↗
PubMed1978

Polynucleotides. LVI. Synthesis and properties of poly(2-deoxy-2'-fluoroinosinic acid).

Poly (2'-deoxy-2'-fluoroinosinic acid) [ poly(If)] was synthesized by polymerization of 2'-deoxy-2'-fluoroinosine 5'-diphosphate catalyzed by Escherichia coli polynucleotide phosphorylase. Although the UV absorption properties of poly(If) closely resembled those of poly(I), thermal melting curves at Na+ concentrations of 0.15M and 0.75M suggested two ordered structures for poly(If) neutral form. CD psectra taken at 0.15M Na+ concentration showed rather larger amplitudes in both a peak at 273 nm and a trough at 246 nm, suggesting rather strong vertical stacking of bases. When complexed with poly(C), poly(If) forms a double-stranded complex, poly(If).poly(C) which has Tm's higher by 10-20 degrees than those of poly(If).poly(C) measured under the same conditions. The CD spectrum of this complex resembled that of poly(I).poly(C). The effect of the fluorine atom at the 2'-position on thermal stability of polynucleotides is discussed.

Circular Dichroism↗
PubMed1977

Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid).

Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.

Aza Compounds↗
PubMed1977

Polynucleotides. L. Synthesis and properties of poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid).

Poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid) were synthesized from the corresponding diphosphates with the aid of polynucleotide phosphorylase from E. coli. UV, CD, acid titration and mixing with poly (U) were investigated. Comparing these properties with those of poly (A) and poly (2'-azido-2'-deoxyadenylic acid), it was found that 2''substituents exert significant effects on the thermal stability of these polynucleotides, though the overall conformational structure was not greatly changed.

Circular Dichroism↗
PubMed1977

Polynucleotides. XLVI. 1 Synthesis and properties of poly (2'-amino-2'-deoxyadenylic acid).

Poly (2'-amino-2'-deoxyadenylic acid) [poly (Aa)] was prepared from chemically synthesized 2'-amino-2'-deoxy-ADP by the catalysis of polynucleotide phosphorylase. Poly (Aa) showed a similar UV absorption spectra to poly (A), but quite different CD spectra at pH 7.0 and 5.7. At the former pH it showed a single negative Cotton band and at the latter a curve with a large splitting of bands. Acid titration of poly (Aa) suggested protonated form below pH 7.0. Temperature absorption profiles and their dependency on sodium ion concentration suggested an ordered structure for poly (Aa) which is stabilized by stacking of bases and intrastrand interaction between 2'-amino and internucleotidic phosphate groups. Poly (Aa) forms a 1:2 complex with poly (U) at neutrality and its Tm was 45 degrees in the presence of 0.15M sodium ion.

Chemical Phenomena↗
PubMed1977

Polynucleotides. XLV Synthesis and properties of poly(2'-azido-2'-deoxyinosinic acid).

Poly (2'-azido-2'-deoxyinosinic acid), [poly (Iz)], was synthesized from 2'-azido-2'-deoxyinosine diphosphate by the action of polynucleotide phosphorylase. Poly (Iz) has UV absorption properties similar to poly (I) and hypochromicity of 11% at 0.15M Na+ and neutrality. In solutions of high Na+ ion concentration, poly (Iz) forms a multi-stranded complex and its Tm at 1.0M Na+ ion concentration was 43 degrees. Upon mixing with poly (C), poly (Iz) forms a 1:1 complex having a Tm lower than that of poly (I)-poly (C) complex in the same conditions. The effect of substitution at the 2'-position of the poly (I) strand was discussed in relation to the interferon-inducing activity.

Azides↗
PubMed1976

Polynucleotides. XL. Synthesis and properties of poly 2'-azido-2'-deoxyadenylic acid.

Poly 2'-azido-2'-deoxyadenylic acid (Poly Az) was synthesized from 2'-azido-2'-deoxyadenosine diphosphate by polynucleotide phosphorylase. Poly (Az) has U.V. absorption properties similar to poly (A) and hypochromicity of 40% at 0.1 M Na+ and neutrality. CD curve also resembled to that of poly (A), but has smaller ellipticity. Titration of poly (Az) with HCl gave a transition at pH 5.5, but exact structure of the acid-form complex was not elucidated. Upon mixing with poly (U), poly (Az) forms a 1:1 and 1:2 complexes having Tm's somewhat higher than that of poly (A)- poly (U) complex in the same condition.

Azides↗
PubMedDate not supplied

Template activity of poly(2'-fluoro-2'-deoxyinosinic acid) for murine leukemia virus reverse transcriptase.

The 2'-substituted analog of poly(inosinic acid) ((I)n), poly(2'-fluoro-2'-deoxyinosinic acid) ((dIfl)n) served as an effective template for the RNA-directed DNA polymerase (reverse transcriptase) from Moloney murine leukemia virus. When assayed under the same conditions, the parent compound (I)n showed little, if any, template activity. In the presence of other templates, i.e. poly (2-O-methylcytidylic acid), (dIfl)n could also assume the role of primer for the reverse transcriptase reaction, whereas, again, (I)n failed to do so.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Inhibitory effect of tannins on reverse transcriptase from RNA tumor virus.

Twenty-four tannins and related compounds were examined for inhibition against reverse transcriptase from RNA tumor virus. Hydrolyzable tannins showed a potent inhibitory effect comparable to nitidine, in the presence of polyadenylic acid-oligothymidylic acid as a template-primer. A lesser inhibitory activity was observed for the monomeric ellagitannins, gallotannins, and nitidine using polycytidylic acid-oligodeoxyguanylic acid as a template-primer, whereas the inhibitory activity of dimeric ellagitannins was almost as potent as that observed for these compounds in the polyadenylic acid-oligothymidylic acid directed reaction. Inhibition by tannins was reversed by the addition of either template-primer or enzyme, suggesting that the inhibition is due to the interaction of tannins with both of them.

Animals↗