Altered Nucleic Acid Research Articles

Studies on chemical alterations of nucleic acids and their components—IX : Synthesis and reaction of 1-aminoadenosine and related compounds

Adenosine and its related compounds reacted with hydroxylamine-O-esters to give the corresponding 1-amino derivatives. 1-Amino-adenines were rearranged in the presence of alkali to afford 5(4) - amino - 4(5) - (1,2,4 - triazol - 3 - yl) - imidazole. 1-Amino derivatives reacted with ethyl orthoformate to give 7H - s - triazolo[3,2 - i] - purine derivatives and with H 2S to give 1 - amino - 6 - mercaptopurines. All the 1-amino derivatives were readily deaminated to the parental adenines by treatment with NaNO 2.

Studies on chemical alterations of nucleic acids and their components. X. Syntheses and reactivities of 3-aminopyrimidine nucleosides.

Treatment of pyrimidine nucleosides with hydroxylamine-O-esters (or hydroxylamine-O-aryl ethers) produced the corresponding 3-amino derivatives. 3-Aminouridine derivatives underwent deamination and acetylation to give uridines and 3-acetamidouridines, respectively. 3-Aminocytidine derivatives underwent, in addition to deamination, replacement with a sulfhydryl and cyclization with an orthoformate to give 3-amino-4-thiouridine and 1, 2, 4-triazolo [2, 3-c] pyrimid-5 (6H)-one derivatives, respectively. Proton magnetic resonance and ultraviolet data of 3-amino derivatives are tabulated.

Studies on chemical alterations of nucleic acids and their components. VIII. Alkaline rearrangement of 1-aminoadenosine to 5-amino-1-.BETA.-D-ribofuranosyl-4-(1,2,4-triazol-3-yl)imidazole.

Studies on chemical alterations of nucleic acids and their components. VIII. Alkaline rearrangement of 1-aminoadenosine to 5-amino-1-.BETA.-D-ribofuranosyl-4-(1,2,4-triazol-3-yl)imidazole.

Studies on chemical alterations of nucleic acids and their components—VII : C-Alkylation of purine bases through free radical process catalyzed by ferrous ion

Guanine, guanosine, and 5′-guanylic acid were methylated with t-butylhydroperoxide in the presence of ferrous ion to give the corresponding 8-Me derivatives in fairly good yields. Adenine, hypoxanthine, and their ribosides also underwent the methylation to give the corresponding mono- and di-methyl derivatives where Me groups were substituted in position-2, -8, or both. N,N-Dimethylcarbamoyl group was introduced to position-8 of guanosine under a similar condition using dimethylformamide as the reaction solvent.

Studies on chemical alterations of nucleic acids and their components. VI. N-amination of some nucleic acid bases containing basic nitrogen with hydroxylamine-o-esters

Studies on chemical alterations of nucleic acids and their components. VI. N-amination of some nucleic acid bases containing basic nitrogen with hydroxylamine-o-esters

Studies on chemical alterations of nucleic acids and their components. V. Amination reaction of 1,3-dimethyluracil with hydroxylamine-o-sulfonic acid

Studies on chemical alterations of nucleic acids and their components. V. Amination reaction of 1,3-dimethyluracil with hydroxylamine-o-sulfonic acid

Head Size and DNA Content in Bacteriophage T4

The control of form or shape inheritance can be approached by studying the morphogenesis of bacterial viruses. Shape variants of bacteriophage T4 with altered protein shell (capsid) size and nucleic acid (DNA) content have been found by electron microscopy, and a mutant (E920g in gene 66) controlling head size has been described. This mutant produces short-headed particles which contain 2/3 the normal DNA content and which are non-viable when only one particle infects a cell (Fig. 1).We report here the isolation of a new mutant (191c) which also appears to be in gene 66 but at a site distinct from E920g. The most striking phenotype of the mutant is the production of about 10% of the phage yield as “giant” virus particles, from 3 to 8 times longer than normal phage (Fig. 2).

Instability of fluorenylamine-substituted polynucleotides: Loss of carcinogen and production of an altered nucleic acid

Reaction of N-hydroxy-2-aminofluorene (N-OH-AF) with rRNA at pH 5.0 decreased the molecular weight of the polynucleotide. Toluene-soluble aryl derivatives were released on hydrolysis of fluorenylamine- and biphenylamine-substituted RNA by treatment with venom phosphodiesterase and alkaline phosphatase.These data suggested that arylhydroxylamines, activated by incubation at pH 5.0 or by enzymatic O-acetylation, might react with the phosphate group of RNA to give unstable phosphate triesters. Spontaneous hydrolysis of these triesters would result in cleavage of the polynucleotide chain. Further enzymatic hydrolysis of the phosphate esters would yield nonpolar arylamine derivatives.Enzymatically degraded 4-aminobiphenyl(ABP)-RNA adducts were examined by high performance liquid chromatography (HPLC) for the presence of a putative phosphorylated adduct. Synthetic standards of the C-8-guanosine monophosphate-ABP adduct (ABP-GMP) and o-aminobiphenyl-O-phosphate were used as markers in the analysis of the digested RNA. A phosphate adduct of ABP was undetectable by these methods. The data also indicated that the ABP-GMP formed in the acyltransferase-mediated binding of N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) to RNA is readily degraded during the enzymatic digestion of the RNA adduct.

Effects of Maternal Dietary Lipotropes on Prenatal and Neonatal Rats ,

The purpose of this study was to investigate the effects of severe and marginal deficiencies of lipotropes on the developing rat embryo. Groups of female rats were fed diets varying in methionine and choline content with and without vitamin B12. The diet low in choline and methionine supplemented with vitamin B12 constituted a marginally deficient diet which supported conception, implantation, and fetal growth in a normal fashion and prevented neonatal hydrocephaly. Without vitamin B12 supplements, even when the diet contained normal amounts of choline and methionine, congenital anomalies and alterations in nucleic acids and protein of brain and liver were observed at various periods of development. Although the marginally deficient newborn offspring appeared clinically normal, biochemical determinations indicated smaller brain cells and irregularities in protein synthesis. It appears from these results that prenatal maternal nutrition can have an adverse effect on the newborn which may carry over into postnatal life.

In vivo and in vitro demonstration of nuclear bodies in vaccinia infected cells

Nuclear bodies have been found in hypertrophic human epidermal cells infected in vivo with vaccinia virus. A hypothetical cycle of development and subdivision of these structures is presented. WI-26 human fibroblasts, infected in vitro with the vaccinia virus isolated from biopsy specimens, also contain “nuclear bodies” in cells which evidence viral cytopathic changes. Since vaccinia virus and all other viruses associated with the occurrence of nuclear bodies are DNA viruses, it is suggested that the process of viral replication with its concomitant altered nucleic acid metabolism and associated specific protein synthesis results in the production of nuclear bodies.

Base alterations of nucleic acids in stomach wall after prolonged atropine treatment

The base composition and quantitative alterations in purine and pyrimidine of ribonucleic (RNA) and deoxyribonucleic acid (DNA) have been studied in the glandular (pyloric) and membranous (rumenal parts of the rat stomach after prolonged atropine treatment. Prolonged atropine treatment produced alterations in both composition and total quantities of purine and pyrimidine bases of RNA in the membranous and glandular parts of the rat stomach, while the purine and pyrimidine bases of DNA were altered only quantitatively. Alterations in base composition and quantities of purine and pyrimidine bases of RNA were only reversible in the membranous part of the stomach in 10 days after cessation of treatment.

Altered nucleic acid metabolism in human cell cultures infected with mycoplasma.

Altered nucleic acid metabolism in human cell cultures infected with mycoplasma.

Mutant male strains with an altered nucleic acid pump

Mutant male strains with an altered nucleic acid pump

Mutagenic and Inactivating DNA Alterations

typic consequences has greatly benefited from the advancement of biochemical and genetic methods. 1. The alteration of nucleic acid bases can be measured by UV,1 infrared and nuclear magnetic spectra, use of radioactive bases in nucleic acids, chromatography, and straightforward chemistry. Cross-linking can be shown by reversible DNA denaturation, and backbone breakage by decreases in the sedimentation constant, viscosity, or light scattering. To uncover the primary site of attack and the high specificity of some chemicals toward nucleic acids, synthetic oligo- and polynucleotides will have to be increasingly used. 2. The methods for determining the phenotypic consequences of nucleic acid alterations range far afield. Chromosomal breaks and large chromosomal alterations can be determined cytologically or by classical genetic methods. The extent and specificity of small nucleic acid alterations can be analyzed both by genetic fine structure measurements and by the specificity of forward and reverse mutation induction. The correlation between nucleic acid alterations and genetic investigations has been possible mainly by the use of viruses or transforming DNA for which the effect of chemicals can be safely attributed to the direct effect on nucleic acids. Finally, the analysis of mutagenic nucleic acid alterations can be used, together with in vitro experiments on protein synthesis, to determine the base sequence of some genetic regions. The consistency of these results checks in turn the validity of the genetic and biochemical conclusions.

EFFECT OF 5-FLUOROURACIL ON ANTIGENIC PROPERTIES OF TOBACCO MOSAIC VIRUS.

INCORPORATION of 5-fluorouracil (FU) into TMV particles is claimed to exert a number of biological effects. Although the ability to initiate local lesions by equal quantities of normal and FU substituted virus is not significantly different, less virus is produced in a systemic host when substituted TMV is used as the inoculum1. Another aspect of FU incorporation is the increased sensitivity of substituted virus towards ultra-violet irradiation2. In the last case at least, the biological response could be traced to the altered nucleic acid component of the virus, in analogy to biological systems of higher organization3,4.

Alterations in nucleic acids during hepatoma formation in rats fed p-dimethylaminoazobenzene

Alterations in nucleic acids during hepatoma formation in rats fed p-dimethylaminoazobenzene