PubMed Health⌕ Search

Biomedical subjects

P Walsmann

Publications and source records attributed to P Walsmann.

At least 19 recordsLinked to original sources
PubMed1991

Structure-activity relationships of recombinant hirudins.

The complex formation between thrombin and hirudin is unique among other serine proteinase-inhibitor complexes. The serpines occupy the specificity pocket of the active site of the target enzyme with an amino acid residue corresponding to the specificity of the enzyme at the P1 site of the substrate. In contrast, the Thr2 residue of hirudin approaches only the entrance of the pocket. The peptide chain of the inhibitors D-Phe-Pro-ArgCH2Cl and NAPAP is antiparallel to the enzyme backbone, whereas the N-terminal amino acids of hirudin run parallel. These unexpected interactions seem to contribute to a greater extent to the tight binding than the ionic interactions of the hirudin tail with the fibrinogen binding site of thrombin. Obviously, these interactions account for the unique selectivity of hirudin for thrombin.

Amino Acid Sequence↗
PubMed1991

Isolation and characterization of a thrombin inhibitor from the tick ixodes ricinus.

The secretion of the salivary glands of ticks, Ixodes ricinus, contains anticoagulant substances. Some years ago an antithromboplastin, ixodin, was described. The present paper refers the isolation and characterization of a second anticoagulant substance of the ticks named ixin. Ixin proved to be a relatively stable and specific thrombin inhibitor. The multi step procedure for isolation results in a 850-fold purification. The preparation obtained has a specific activity of 250 antithrombin units/mg. It is not homogeneous and still contaminated. The substance was assumed to be a miniprotein.

Amides↗
PubMed1990

Preparation of dextran-bound recombinant hirudin and its pharmacokinetic behaviour.

Recombinant desulphatohirudin was bound via lysine residues to oxidized dextrans. The hirudin-dextran conjugates inhibit thrombin like free hirudin. The Ki-values are in the same range. In rabbits and rats the pharmacokinetic behaviour following i.v. administration of these conjugates was examined in comparison to that of hirudin. The hirudin-dextran conjugates were more slowly eliminated than hirudin, the distribution volumes in steady-state were significantly reduced, and, in comparison to hirudin, 5 to 15 times larger areas under the plasma concentration-time-curves were obtained.

Animals↗
PubMed1989

[Recent developments in the biochemistry of hirudins].

The paper reviews both the isolation methods of native hirudin and the manufacturing process of recombinant hirudins as well as the primary structures of the different hirudin variants. Furthermore, the review presents an evaluation of current studies in the mechanisms of the antithrombin action of hirudin.

Amino Acid Sequence↗
PubMed1988

Quality control of 125I-labelled fibrinogen of various species.

The modified chloramine-T method used for radioiodination of human, rat, and bovine fibrinogen guaranteed mild labelling conditions and a satisfactory labelling efficiency. The quality of the 125I-human, rat, and bovine fibrinogen preparations obtained met the requirements with respect to clottability, low content of 125Iodide as well as in vitro and in vivo stability.

Animals↗
PubMed1988

Hirudin as a diagnostic agent.

The high specificity and strong affinity of hirudin for thrombin enables the inhibitor to interfere with most effects of this enzyme. The paper reviews the usage of the inhibitor for diagnostic and experimental-scientific purposes.

Animals↗
PubMed1988

Evidence for the identity of hirudin isolated after kidney passage with the starting material.

Natural, sulfated and recombinant, non-sulfated hirudin preparations re-isolated from urine after kidney passage were compared with the corresponding administered preparations by reversed-phase high-performance liquid chromatography, and by amino acid sequence and composition analysis. It could be demonstrated that the hirudins were excreted in unmodified form. Natural hirudin could be fractionated by the chromatographic system used into a large number of isoinhibitor forms, some of which were shown to differ from each other in their amino acid sequence.

Amino Acid Sequence↗
PubMed1988

Pharmacokinetics of 125I-hirudin in rats and dogs.

Hirudin was 125I-labelled using a modified chloramine-T method. 125I-hirudin proved to be a suitable marker in pharmacokinetic studies, if unchanged 125I-hirudin in body fluids was determined by means of a binding assay using immobilized thrombin. In rats and dogs a study was performed on the pharmacokinetic behaviour of hirudin following intravenous and subcutaneous injection, resp., or one-hour infusion and pharmacokinetic parameters were calculated.

Animals↗
PubMed1988

[Synthetic inhibitors of serine proteinases. 34. The effect of modification of the amidino function of N-alpha-substituted 4-amidinophenylalanine amides on inhibitory activity].

Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are selective inhibitors of thrombin. The exchange of the amidino function for an aminomethyl residue does not influence the selectivity and potency of their inhibitory activity. In contrast, the modification of the amidino function of the N alpha-arylsulfonylaminoacylated compound N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide results in a drastic loss of inhibitory activity. Only the oxamidino derivative possesses considerable high affinity for thrombin. Obviously, in tight binding inhibitors of thrombin structural variation results in any case in a loss of inhibitory activity.

Amidines↗
PubMed1987

[Synthetic inhibitors of serine proteinases. 32. Inhibition of trypsin, plasmin and thrombin by amides of N-alpha-substituted 4-amidinophenylalanine. Effect of various amino acids and blocking groups of the n-alpha residue on inhibitory activity].

Cyclic amides of N alpha-arylsulfonylated 4-amidinophenylalanine are specific, highly potent inhibitors of thrombin. Introduction of amino acids between the arylsulfonyl blocking group and amino nitrogen influence particularly the antithrombin activity. By the use of glycine as spacer the compounds become tight binding thrombin inhibitors, while introduction of other omega-amino acids, Gly-Gly, L-Pro, Gly-L-Pro or L-Pro-Gly, reduces the specificity and potency of thrombin inhibition. Substitution of the arylsulfonyl blocking group for a heteroarylsulfonyl residue or an aryl residue causes a decrease in antithrombin activity, while substitution for a benzoyloxycarbonyl blocking group has only slight influence. It is concluded that the N alpha-moiety is of decisive importance for the antithrombin activity of derivatives of 4-amidinophenylalanine.

Amidines↗
PubMed1987

Studies on the pharmacokinetics of hirudin.

Absorption, distribution and elimination of the naturally occurring thrombin inhibitor hirudin were studied in dogs after intravenous and subcutaneous injection or intraduodenal application using an assay which detects the inhibitor in blood and urine by its antithrombin activity. The plasma concentration time curve after intravenous injection of the pure polypeptide could be best described by an open two-compartment model with first-order kinetics. Dependent on the dose, long-term infusion or subcutaneous injection produced anticoagulantly effective blood levels for a prolonged period of time. The enteral absorption is very low and does not suffice to produce adequate blood levels. Hirudin is distributed into the extracellular space and eliminated through the kidneys by glomerular filtration in active form with a half-time of about 1 h.

Administration, Oral↗