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Biomedical subjects

C Bergmann

Publications and source records attributed to C Bergmann.

66 records · Page 4Linked to original sources

Chemical synthesis and expression of a gene coding for hirudin, the thrombin-specific inhibitor from the leech Hirudo medicinalis.

A DNA containing the coding sequence for the proteinase inhibitor protein hirudin from the leech Hirudo medicinalis has been obtained by enzymic ligation of chemically synthesized deoxyoligonucleotides. The 226 bp synthetic gene carries signals for the translation initiation and termination. Fragment synthesis was performed by the Khorana ligation method as well as by the fill-in method. Efficiencies of these two methods are compared. The synthetic gene was expressed in E. coli as a fusion protein with beta-galactosidase under the control of the lac-promoter as well as a non-hybrid protein under the control of the lambda PL-promoter. The non-hybrid expression product was shown to have similar biological properties as the authentic protein isolated from the leech.

Amino Acid Sequence↗

[In vivo antitumor activity of hydrosoluble derivatives of 7-hydroxycholesterols].

Sodium bis-hemisuccinates of 7 beta- and 7 alpha-hydroxycholesterols are moderately water-soluble. They have been tested intraperitoneally against the murine Krebs-II carcinoma, grown as an ascitic tumour, and their action has been compared with that of usual chemotherapeutic drugs, cyclophosphamide, 5-fluoro-uracil, and methotrexate. The hydroxycholesterol derivatives show a faster and stronger activity (life prolongation), and lead to the complete disappearance of the tumour in about 1/3 of the cases, even with one single injection. Similar results have been obtained (on fewer cases) with two other experimental ascitic tumours, the S-180 sarcoma and the ZHC hepatoma. The mechanism of action is not known; it appears to be very different from that of the usual anti-cancer chemotherapeutic agents.

Animals↗

Inhibitors of hydrogen peroxide-induced haemolysis of bovine erythrocytes.

The optimal conditions for the haemolysis of bovine erythrocytes by H2O2 have been established. The parameters were concentration of erythrocytes, H2O2 concentration, time, and influence of the solvent in which the substances tested were dissolved. Some inhibitors of this oxidative haemolysis have been employed to serve as model substances for further antihaemolytic investigations with natural products.

Acetates↗

The importance of serum lipoproteins in the cytolytic action of 7 beta-hydroxycholesterol on cultured hepatoma cells.

The toxicity of 7 beta-hydroxycholesterol for cultured HTC cells is 10 times greater if serum lipids and lipoproteins are absent from the culture medium. A water-soluble derivative of 7 beta-hydroxycholesterol, sodium 3,7-bishemisuccinate, showed the same toxicity as the original molecule and was also 8 times more toxic when serum lipids and lipoproteins were absent. But the rapid inhibition of DNA synthesis was similar in cells treated with both compounds, whether lipids and lipoproteins are present or not. Thus the absence of serum lipids and lipoproteins enhances the lytic effect of both substances but does not increase their intracellular action on DNA synthesis. This first parallel study on lipophilic 7 beta-hydroxycholesterol and its water-soluble homologue shows the importance of the serum lipids and lipoproteins in the cytotoxicity of such sterols.

Animals↗

Binding of tRNA in different functional states to Escherichia coli ribosomes as measured by velocity sedimentation.

The binding of initiator and elongator tRNAs to 70-S ribosomes and the 30-S subunits was followed by velocity sedimentation in the analytical ultracentrifuge. fMet-tRNAfMet binds to A-U-G-programmed 30-S subunits, but not to free or misprogrammed particles. Both the formylmethione residue and the initiation factors increase the stability of the 30-S x A-U-G x fMet-tRNAfMet complex. fMet-tRNAfMet is bound only to the P site of the 70-S ribosome even in the absence of A-U-G. Two copies of tRNAPhe or Phe-tRNAPhe are bound to the ribosome with similar affinity. In contrast to a recent report [Rheinberger et al. (1981) Proc. Natl Acad. Sci. USA, 78, 5310-5314], it is shown that three copies of tRNA cannot be bound simultaneously to the ribosome with binding constants higher than 2 x 10(4) M-1. Phe-tRNAPhe when present as the ternary complex Phe-tRNAPhe. EF-Tu x guanosine 5'-[beta,gamma-methylene]triphosphate binds exclusively to the A site. The peptidyl-tRNA analogue, acetylphenylalanine-tRNA, can occupy both ribosomal centers, albeit with a more than tenfold higher affinity for the P site. The thermodynamic data obtained under equilibrium conditions confirm the present view of two tRNA binding sites on the ribosome. The association constants determined are discussed in relation to the mechanism of ribosomal protein synthesis.

Binding Sites↗