Adolf Wacker

Thymin-dimerisierung und Überlebensrate bei bakterien

On giving small doses of u.v. irradiation at 254 m μ , to resting or synchronously dividing bacterial cells a correlation is found between rate of death and thymine dimerization : the bacterial suspension with fewer survivors contains more thymine dimers. With an equal u.v. dose more thymine is dimerized in denatured single-stranded DNA than in native double-stranded DNA.

Photochemische reaktionen von uracil und uridin

On u.v.-irradiation of uracil and uridine a water addition-product and a dimer are formed in each case. When a mixture of uracil and thymine is irradiated a mixed dimer can be isolated, which consists of uracil and thymine. The formation, isolation and stability of the irradiated compounds are discussed. The irradiation products of uracil and uridine are not growth factors for the uracil-deflcient mutant E. coli 63–86.

Über die strahlensensibilisierende wirkung des 5-bromuracils†

5-Bromouracil and 5-bromodeoxyuridine are hardly altered by u.v.-irradiation (in water or in ice). On the other hand 5-bromouracil, which is incorporated in deoxyribonucleic acid, is dehalogenated to a great extent. The amount of thymine dimer formed in bacterial DNA by u.v.-irradiation decreases after incorporation of 5-bromouracil.

Some structural requirements for the antibiotic action of distamycins.

In some recent publications [6,7] we have reported the reaction of this antibiotic on the structure and template activity of DNA. The absorbance of DNA decreases in the presence of distamycin A. This effect is dependent on the antibiotic/DNA-P ratio (r). The melting profile of native DNA shifts towards higher temperatures with increasing antibiotic concentration. The hyperchromicity also increases from 40 to about 60% in the presence of distamycin when r is raised from r = 0 to r = 1 [6]. These interactions lead to pronounced inhibition of the incorporation of AMP into RNA in the DNA directed RNA-polymerase system. The structure of this antibiotic also obtained by total synthesis [8] , is characterized by three residues of 1 -methyl-4-aminopyrrole-2-carboxylic acid and two side chains, the first constituted by a formyl group, and the second by a propionamidine chain (fig. 1). Arcamone et al. [9, lo] have recently succeeded in in synthesizing some structural analogues of dista-

Template specific inhibition of DNA polymerases from RNA tumor viruses by distamycin A and its structural analogues

Distarnycin A (D&/A) is an antiviral antibiotic which was shown to be active against several DNA viruses [l-3] and to inhibit the synthesis of adaptive enzymes in bacteria [4]. Experimental studies suggest that D&/A blocks some early steps in the growth cycle of DNA viruses, probably connected with DNA replication [S] . This mechanism correlates well with the ability of Dlst/A to bind to doublestranded and single-stranded DNA [6,7] and to inhibit the template activity of DNA for DNA [8] and RNA [7] polymerases. The structure of Dist/A is characterized by 3 residues of 1 -methyl-4-aminopyrrole-2-carboxylic acid and 2 side chains (fig. 1). Some structural analogues of Dist/A have been recently synthesized [9] by varying the number of pyrrole residues in the molecule. Chandra et al. [lo] have shown that the analogues containing 4 (Dist/4) and 5 (Distl5) pyrrole rings are more active than the parent compound on vaccinia virus and in the DNA-dependent RNA polymerase reaction. It is known that RNA-oncogenic viruses require DNA synthesis for their replication. This

Influence of tilorone hydrochloride on the secondary structure and template activity of DNA

The dihydro-chloride salt of 2,7-bis(2-(diethylamino)ethoxy)-fluoren-9-one, referred to as tilorone hydrochloride (non-proprietary name) or bis-DEAEfluorenone, is a broad spectrum antiviral compound [l] with antitumor activity [2,3]. Mayer and coworkers [4,5] have identified this compound as an interferon inducer and estabilished a relationship with the antiviral activity. Chandra et al. [6] have recently reported the inhibition of DNA polymerase activity in RNA tumor viruses by tilorone hydrochloride. This inhibition was found to be selectively dependent on the type of primer-template used in the enzymatic reaction. It was therefore interesting to study the mechanism of tilorone hydrochloride interaction to DNA, and its consequence on the template activity of DNA in DNAand RNA-polymerase systems.

Über den Einbau Purin-analoger Verbindungen in die Bakterien-Nukleinsäure

2-Aminopurine is transformed by E. coli B into adenine and guanine. Both metabolites are used for nucleic acid synthesis, while only a small quantity of unchanged 2-aminopurine is incorporated into DNA and RNA. Adenine or guanine diminish the uptake of 2-aminopurine. E. coli B converts purine to adenine and guanine. Unchanged purine could not be detected in the bacterial nucleic acids.

Some structural requirements for the antibiotic action of distamycins II. Structural modification of the side chains in distamycin A molecule

Distamycin A, an antibiotic substance produced by Streptomyces distallicus, is endowed with cytostatic properties evidenced by its activity on some experimental tumors of the mouse and the rat [l] . It suppresses the multiplication of T, and T, phages in E. coli K12 [2] and interferes with the multiplication of some DNA-viruses such as vaccinia, herpes simplex and adenoviruses [3] , Another interesting feature of distamycin A is its ability to prevent the induction of bacterial adaptive enzymes of E. coli [4,5]. In some recent publications [6,7] we have reported the reaction of this antibiotic on the structure and template activity of DNA. The absorbance of DNA decreases in the presence of distamycin A. This effect is dependent on the antibiotic/DNA-P ratio (r). The melting profile of native DNA shifts towards higher temperatures with increasing antibiotic concentration. The hyperchromicity also increases from 40 to about 60% in the presence of distamycin when r is raised from r=O to r=l [6]. These interactions lead to a pronounced inhibition of the incorporation of AMP into RNA in the DNA-directed RNA-polymerase system. The structure of this antibiotic also obtained by

Kondensationsprodukte von Oxyketonen und Aminoketonen mit 2,4,5-Triamino-6-oxy-pyrimidin

By condensing 2:4:5-triamino-6-hydroxy-pyrimidine with dihydroxyacetone (diacetate), diaminoacetone or acetone-1,3-di (p-formylaminobenzoic acid) not the expected 8- or 9-oxymethyl resp. -aminomethyl-pteridines but 8-or 9-methyl-pteridines were obtained. With p-tolyl-d-isoglucosamine not a tetrahydroxybutyl-pteridine but a trihydroxybutyl-pteridine was formed. For an explanation of these results it is supposed that from the dihydro-pteridines formed at first by intramolecular splitting off of H2O or R·NH2 aromatization takes place.

UV-resistenz azathymin-haltiger bakterienzellen

Bacterial cells in which the thymine of the DNA is partially replaced by 6-azathymine exhibit increased resistance to u.v. irradiation.