Zeitschrift fur Naturforschung. Section C, Biosciences最新文献

A minimal topological difference (MTD) approach is made to describe quantitative structure-activity relationships (QSAR) for the Na+, K+-ATPase inhibitory activity of cardiotonic steroids. The calculations take into account 20 derivatives of digitoxigenin, digoxigenin, and gitoxigenin with small substituents at different sites of the steroid backbone. A multiple correlation coefficient of r = 0.916 is obtained using the MTD and an indicator variable for the presence of a 15 beta substituent. The corresponding receptor map reveals receptor wall vertices in the C11, C12, C15, and C22 regions. Both 3 beta and 16 beta substituents are found to contain receptor cavity vertices. The MTD results are discussed with respect to lactone-ring conformational investigations presented and they are compared with findings of previous structure-activity studies.

The antiproliferative activity of divers ferricenium complexes [Cp2Fe]+X-(X- = [CC13COO]- X CC13COOH (I); X- = [CC13COOH]- X 2 CC13COOH (II); X- = 1/2 [C13FeOFeC13]2- (III); X- = [FeC14]- (IV); X- = [2,4,6-(NO2)3C6H2O]- (V)) was investigated against solid, subcutaneously growing Ehrlich ascites tumor (EAT) in vivo as well as against EAT cells cultivated in vitro as permanent suspension culture. In vivo, triple intraperitoneal injections of the complexes II (3 X 200 mg/kg), III (3 X 100, 140, 180 mg/kg) or IV (3 X 160 mg/kg) markedly suppressed tumor development thus that the sizes of treated tumors were reduced to 42-48% related to control tumors (100%); these results point to the systemic character of the antitumor action by ferricenium complexes in vivo. In vitro, all ferricenium complexes inhibited cellular proliferation to an equal extent; application of 10(-5) M diminished the increase in cell number by 20-40%, application of 10(-4) M resulted in a total cessation of cellular proliferation. In comparison to cis-diamminedichloroplatinum(II), the cell growth-inhibiting effect of ferricenium complexes was less pronounced and required 10- to 50-fold higher concentration levels to evoke equivalent cytostasis.

There are non-random features in the occurrences of nucleotides in the DNA's of certain organisms which are detectable by statistical analyses of the entire sequence. Earlier, using the bacteriophage Phi-X 174 DNA sequence, we had reported that the self-information values for one type of dinucleotide association showed a marked periodicity when their autocorrelation coefficients were graphed. A similar, but computationally simpler, analysis has been developed which gives a comparable indication of periodicity. The difference, in average autocorrelation coefficients obtained with this analysis, between the peak values and all others has been used as an index to compare the extent of periodic non-randomness for a series of natural DNA sequences and for various artificial sequences. Calculations show that triplet periodicity, the relationship between dinucleotides separated by a single nucleotide, is characteristic only of the natural sequences of certain filamentous phages and is not found prominently in any other DNA analyzed (including sequences of similar length from plasmids, yeast, bacteria and higher animals). By shuffling nucleotides in a given sequence or by substituting selected nucleotides to alter various positions in both periodic and aperiodic sequences, we have found that an excess or deficiency of a given nucleotide at one of the three positions in a triplet reading frame can simulate the periodic characteristic. Thus, it appears that this global statistical analysis detects the tendency for single-strand phages to utilize a specific nucleotide, rather than one randomly selected, to constitute codons.

Three growth rate experiments involving several sampling points were performed to investigate the previous finding that very low concentrations of HgCl2 inhibit the growth of murine lymphoblasts in vitro. However, results presented here do not confirm this, there being no significant differences between the three independent growth rate experiments.

DNA transfection in mouse L-cells was performed by means of the electropermeabilization technique (U. Zimmermann, G. Pilwat, and F. Riemann, Z. Naturforsch. 29, 304 (1974)). The plasmid pSV 2-neo used leads to neomycin-resistance in stably transfected L-cells. Optimized conditions resulted in high yields of clones at relatively low DNA concentration. The influence of temperature during pulse application and during the subsequent resealing process as well as the field parameters and medium composition are discussed.

We have analysed spermatogenetic cells by flow cytometry to quantify effects of ionizing radiation. The radiation-induced reductions of testicular DNA-synthesizing cells, primary spermatocytes, haploid round and elongated spermatids as well as the increases of numerical chromosome aberrations (abnormal diploid spermatids and aneuploidies) in NMRI inbred mice are described. Testicular weights were determined as a parameter of germ cell decrease, and histologic cross sections of the testes were analysed. Since even an exposure of 0.05 Gy (= 5 rad) may be detected by a reduction of DNA-synthesizing cells (Acta Radiol. Oncol. Radiat. Phys. Biol. 21, 349-351 (1982) [1]), the use of the in vivo system "spermatogenesis" as a biological dosimeter to monitor low dose effects and to determine RBE values of different radiation qualities is suggested.

Propylglyoxal bis(guanylhydrazone) sulfate, a novel analog of the well-known antileukemic drug methylglyoxal bis(guanylhydrazone), has been prepared from 2,2-dibromopentanal, and the compound has been characterized biochemically. Although it is a powerful inhibitor of S-adenosylmethionine decarboxylase, its Ki value (0.2 microM) is considerably higher than that of ethylglyoxal bis(guanylhydrazone) (0.06 microM). The compound is only poorly taken up by tumor cells, and its accumulation is not stimulated by a prior exposure of the tumor cells to difluoromethylornithine, a compound that causes polyamine depletion. Thus, the uptake characteristics of the compound are similar to those of ethylglyoxal bis(guanylhydrazone), but in striking contrast to those of methylglyoxal and glyoxal bis(guanylhydrazones). Since the configuration of the double bonds in glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones) has been shown to be identical, the different uptake characteristics are probably only due to differences in side chain size and/or hydrophobicity.

The influence of females on the amount of scent-marking behavior displayed by male Mongolian gerbils was investigated. Males isolated from females scent mark at a low level which increases more than two-fold if females are present in the room for three weeks without direct contact with the males. A similar increase is obtained by application of pooled female urine directly onto the males' noses.

Normal and starved adult chickens were injected intraperitoneally with D-galactosamine hydrochloride (0.5 g/kg body weight) and 6 h later liver chromatin acid-soluble proteins were isolated. These proteins were resolved by a two-dimensional polyacrylamide gel electrophoresis in the presence of non-ionic detergent, Triton X-100, in the first dimension and anionic detergent, sodium dodecyl sulfate, in the second dimension. Although spotting patterns of acid-soluble chromatin proteins were remarkably similar between normal and starved control birds and those receiving D-galactosamine, a disappearance of a 24-kDa protein after administration of this agent was found. Moreover, it was shown that this protein was also completely absent in the chicken erythrocyte chromatin which was known to be inactive in RNA synthesis. It seems that the disappearance of the 24-kDa chromatin protein may be associated with inhibiting of transcription in hen liver after D-galactosamine administration and during hen erythrocyte maturation.

Several model compounds containing thiol and/or amino groups (mercaptoethanol, glutathione, cysteine, ethanolamine, glycine) were studied with respect to their reactivity towards fluorescein isothiocyanate (followed spectrophotometrically at 504 and 412 nm), stability of product and long-wave absorption maximum of the fluorescein residue attached. Thiol groups reacted by far more readily than amino groups. A specific effect was observed with cysteine, indicating an intramolecular transfer of the fluorescein residue from SH to NH2. With sarcoplasmic vesicles both types of reactions were observed. The ratio of products, which can be distinguished by their different stabilities and absorption spectra, depended on the absence or presence of detergents. While with native vesicles the NH2 reaction predominated, with vesicles solubilized with sodium dodecylsulfate, octaethyleneglycol mono-n-dodecyl ether or 1-0-tetradecyl-propanediol-(1,3)-3-phosphorylcholine the SH reaction became prevailing. Already 0.35 mg sodium dodecylsulfate per mg protein were sufficient to give rise to dithiourethane formation exclusively. Excess fluorescein isothiocyanate reacted with several thiol groups of dodecylsulfate-solubilized vesicles. In the presence of ATP binding of fluorescein isothiocyanate to native vesicles was significantly reduced. Total blockage of the vesicular SH groups with N-ethyl-maleimide led to preparations that reacted with fluorescein isothiocyanate much more slowly, compared to native vesicles. Octaethyleneglycol mono-n-dodecyl ether or 1-0-tetradecyl-propanediol-(1,3)-3-phosphorylcholine in the assay accelerated the thioureide formation from N-ethylmaleimide modified vesicles, whereas sodium dodecylsulfate prevented it almost completely. Our results support the suggestion that one or several thiol groups in vicinity of the highly reactive lysyl residue might play a role in the fast specific reaction, which is only observed with intact native vesicles.