[Synthesis of N alpha-(benzoylglycyl)- and N alpha-(benzyloxycarbonylglycyl)-4-amidinophenylalanine amides as thrombin inhibitors].

The 4-nitrophenyl esters of hippuric acid and benzyloxycarbonylglycine had been aminolyzed by racemic 4-cyanphenylalanine into the compounds 3 and 4. After activation as 4-nitrophenyl esters and following reaction with amines the amides 7-14 were formed. These cyano compounds were converted into the amidines via the thioamides 15-22 and the thioimidic esters 23-30.

[Synthesis of N-alpha-benzyloxycarbonyl-4-amidinophenylalanine amides as thrombin inhibitors].

Based on 4-cyanophenylalanine, the title compounds had been obtained by benzyloxycarbonylation of the amino group, subsequent formation of the activated ester by 4-nitrophenol, its aminolysis and at least change of the cyano function to the amidine function via thiocarbamides and thioimid acid esters. The inhibitor effect against thrombin of the pyrrolidid 16 is analogous to those of the adequate N alpha-tosyl compound.

Inhibition of bovine and human thrombins by derivatives of benzamidine.

Thirty-four derivatives of benzamidine were tested for their inhibitory activities on bovine and human thrombins using the chromogenic peptide substrate N-D-Phe-Pip-Arg-pNA. The inhibition constants of small molecular size inhibitors of comparatively low affinity as well as those of tight binding inhibitors did not differ significantly with different species. Accordingly, the active site of bovine thrombin seems to correspond largely to that of human thrombin.

Affinity sorbents containing benzamidine derivatives for biomedical application.

Affinity sorbents for trypsin have been obtained by immobilization of 4-amidinophenylalkylcarboxylic acids on macroporous silica gel. Frontal chromatography was used to measure the dissociation constants of the trypsin-immobilized inhibitor complexes (Kd). The Kd value has been found to increase 50-100 fold on immobilization.

[Computer tomographic diagnosis of endocrine orbitopathy].

On the basis of 52 CT analyses of endocrine orbitopathy the involvement and changes in density and width of the orbital structures are worked out. The differential diagnostic value of CT in inflammatory, tumorous or vascular ophthalmopathy is discussed.

[Synthesis of N alpha-(arylsulfonylglycylglycyl)-4-amidinophenylalanine amides as thrombin inhibitors].

The headline compounds were prepared using N-arylsulfonylglycylglycine-4-nitrophenyl esters. Firstly these compounds were aminolized with 4-cyanphenyl alanine and thereby the N alpha-(arylsulfonylglycylglycyl)-4-cyanphenyl alanines got were transferred into the 4-nitrophenyl esters After aminolysis the desired hydroiodides of the headline compounds starting from the cyano compounds were prepared via the carbamoyl compounds and the thiomidic acid methyl ester hydroiodides. The arylsulfonylglycylglycine rest caused a decreasing of the inhibitor activity.

[Synthesis of N alpha-(tosyl-beta-alanyl)- and N alpha-(tosyl-epsilon-aminocapronyl)amidinophenylalanineamides as strongly effective inhibitors of thrombin].

The headline compounds were prepared for further determination of structure-activity-relationships. By conversion of cyanophenylalanines with the acidic chloride of tosyl-beta-alanine resp. tosyl-epsilon-aminocapronic acid and aminolysis of the following prepared p-nitrophenylic esters the cyano compounds would get the desired structure, which were converted over the thioamides and thioimidic esters in the amidines by the common way.

[Synthesis of N-alpha-(arylsulfonylglycyl)amidinophenylalanine amides as highly active inhibitors of thrombin].

The headline compounds were prepared from purified cyanophenylalanines after presenting arylsulfonylglycyl residues, activation of the carboxyl group by formation of the p- nitrophenylester followed by aminolysis and transfer of a cyano in an amidine function. Besides some esters and an acid were synthetized with the basic structure mentioned in the headline . The p-compounds with a cycloaliphatic amide component proved as "tight binding inhibitors".

[Determination of free and bound ergosterol in microorganisms].

A method for the quantitative determination of free and esterified ergosterol in lipid fractions from biomasses grown on hydrocarbons as sole carbon source is described. Column chromatography was used for the fractionation of lipids. Esterified ergosterol was determined in the benzene fraction and free ergosterol in the methanol fraction by known methods.

[Synthetic serine proteinase inhibitors. 30. Synthesis of alpha-benzoylamino-4-amidinocinnamic acid and alpha-(4-amidinobenzoylamino) cinnamic acid amides, and their inhibitory effect on trypsin-like enzymes].

To test their inhibitory activity against enzymes, the authors synthetized the compounds named in the title. The synthesis started from the corresponding azlactones 1 and 9. Subsequent aminolysis led to the alpha-benzoyl-aminocinnamic acid amides 2 and 10 which contain a cyano function.

Cyclic amides of N alpha-arylsulfonylaminoacylated 4-amidinophenylalanine--tight binding inhibitors of thrombin.

Variation of the potent thrombin inhibitors derived from N alpha-arylsulfonyl-4-amidinophenylalanine was carried out by interposition of an omega-aminoalkylcarboxylic acid between the N alpha-arylsulfonyl residue and the 4-amidinophenylalanine part. The use of glycine as spacer renders the compounds tight binding inhibitors of thrombin. The Ki of the most potent inhibitor reaches the nmol/l range.

[Synthetic inhibitors of serine proteinases. Part 24: Inhibition of trypsin, plasmin and thrombin by cyclic amides of N alpha-arylsulfonylamidinophenyl-glycines (author's transl)].

Cyclic amides of n alpha-arylsulfonyl (3-amidinophenyl)glycine are potent inhibitors of the serine proteinase trypsin, plasmin and thrombin. The weak inhibitory activity of the corresponding 4-amidinophenylglycine derivatives cannot be explained in terms of the structure-activity relationships established for benzamidine derivatives. It might be caused by steric hindrance of enzyme-inhibitor interactions.

Time dependent changes induced by external perturbations on a low molecular weight RNA.

The behaviour of a soluble RNA (MW 19,000) extracted from calf thymus was studied in a partially aqueous solvent. A mixture of dioxane and an aqueous solution of 50 mM NaCl (10:1) was used to dissolve the RNA and the slow optical changes of the solution depending on time and RNA concentration were followed. The relaxation of the RNA was measured after a T-jump in the dioxane-NaCl solvent with an addition of 7 mM methyl red at 470 nm.

Low-intensity two-step absorption of chlorophyll A in vivo.

The intensity-dependent transmission of primary leaves of Triticum aestivum seedlings at lambda = 694 nm was measured with single pulses of a Q-switch ruby laser. At photon flux densities above 2 x 10(17) cm-2s-1 a decrease of transmission was observed. The result is interpreted as a two-step absorption of cooperative units of 10(5)-10(6) chlorophyll molecules.