[70] Trypsin-plasmin inhibitors (Bdellins) from leeches

Fritz, Hans; Krejci, Kaj

doi:10.1016/s0076-6879(76)45073-5

Cited by 24 publications

(17 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include thrombin inhibitors such as hirudin (6) and haemadin (7) and coagulation factor Xa inhibitors such as antistasin (8) and ghilanten (9). The second group of inhibitors acts on the extracellular matrix; these include, for example, bdellins (10), eglins (11), gelin (12), guamerins (13,14), and hirustasin (15).…”

mentioning

confidence: 99%

Theromin, a Novel Leech Thrombin Inhibitor

Salzet¹,

Chopin²,

Baert³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

We purified the most potent thrombin inhibitor described to date from the rhynchobdellid leech Theromyzon tessulatum. Designated theromin, it was purified to apparent homogeneity by gel permeation and anion exchange chromatography followed by two reverse-phase steps of high performance liquid chromatography. The primary sequence of theromin (a homodimer of 67 amino acid residues including 16 cysteine residues) was determined by a combination of reduction and s-␤-pyridylethylation, Edman degradation, trypsin enzymatic digestion, and matrix-assisted laser desorption mass spectrometry measurement. Theromin exhibits no sequence homology with any other thrombin inhibitors. Furthermore, theromin significantly diminishes, in a dose-dependent manner, the level of human granulocyte and monocyte activation induced by lipopolysaccharides. In summary, this potent thrombin inhibitor promises to have high biomedical significance.

show abstract

mentioning

confidence: 99%

Theromin, a Novel Leech Thrombin Inhibitor

Salzet¹,

Chopin²,

Baert³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Re cently, it also has been shown that a syn thetic thrombin inhibitor, MD-805, inhibits the thrombin-induced release of plasmino gen activator from blood vessels [17], Hirudin did not inhibit tPA or urokinase but caused up to 28 % inhibition of plasmin. We have not yet determined whether plas min was inhibited by hirudin itself or by other protease inhibitors present in hirudin preparations [18][19][20]. Two of these contami nants inhibit trypsin and plasmin, while a third inhibits elastase [18,20], In addition, hirudin substantially inactivates bovine fac tor IXa [20], Studies with purified hirudin, isolated by methods such as the one recently described by Walsmann and Markwardt [21], may show whether the inhibition of plasmin in our study was caused by a con taminant.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Fibrinolytic Enzymes by Thrombin Inhibitors

Gilboa

Gb²,

Jw³

1988

Enzyme

View full text Add to dashboard Cite

Thrombin inhibitors have recently advanced to the stage of preclinical testing as anticoagulants. However, little is known about the effects of these inhibitors on the enzymes of the fibrinolytic system. In the present study we evaluated the effect of two protein and two synthetic inhibitors of thrombin on tissue plasminogen activator (tPA), urokinase, and plasmin. We found that hirudin inhibited the amidolytic activity of plasmin but had no effect on tPA or urokinase. Antithrombin III inhibited plasmin and urokinase but had no effect on tPA. D-Phe-Pro-Arg-CH(2)Cl inhibited plasmin and tPA but had no effect on urokinase. Thromstop inhibited all three fibrinolytic enzymes: plasmin, urokinase, and tPA. Thus each thrombin inhibitor tested had different inhibitory effects on the fibrinolytic enzymes. These effects should be carefully considered when thrombin inhibitors are used as antithrombotic drugs.

show abstract

“…Tessulin activity is greater in inhibiting chymotrypsin than guamerin II and hirustasin [18,19]. Tessulin also is a more potent trypsin inhibitor (K i 1 pM) than chymotrypsin, also having higher Ki values than hirustasin [19] and bdellins [14].…”

Section: Fig 5 Action Of Tessulin Therin and Theromin On The Lps Amentioning

confidence: 99%

“…Of two groups of serine-protease inhibitors, one is related to specific inhibitors of proteases interfering in the activation of blood clotting processes, thrombin inhibitors, i.e., hirudin [10], haemendin [11] and inhibitors of factor Xa, i.e., antistasin [12] or ghilanten [13]. The second group is related to inhibitors of proteases acting on the extracellular matrix, i.e., bdellin [14], eglin [15], gelin [16], guamerins [17,18] and hirustasin [19]. However, some of these inhibitors exhibit different amino acid sequences and inhibitory activities; their three-dimensional structures share the same structural motif with the leech antihemostatic protein (L.A.P.)…”

mentioning

confidence: 99%

Amino‐acid‐sequence determination and biological activity of tessulin, a naturally occurring trypsin‐chymotrypsin inhibitor isolated from the leech Theromyzon tessulatum

Chopin¹,

Stefano

1998

European Journal of Biochemistry

View full text Add to dashboard Cite

We purified a new trypsinϪchymotrypsin inhibitor, designated tessulin, from the rhynchobdellid leech Theromyzon tessulatum. This 9-kDa peptide was purified to apparent homogeneity by gel-permeation and anion-exchange chromatographies followed by reverse-phase HPLC. The structure of tessulin was determined by reduction, S-β-pyridylethylation, trypsin digestion, automated Edman degradation and matrix-assisted laser desorption mass spectrometry (m/z 8985 Da). The 81-amino-acid peptide possesses 16 cysteines and exhibits a 16% sequence similarity with antistasin-type inhibitors. Tessulin inhibits trypsin (K i 1 pM) and chymotrypsin (K i 150 pM) and exhibits no activity with thrombin, factor Xa, cathepsin G and elastase. This is the first trypsinϪchymotrypsin inhibitor isolated from leeches that does not inhibit elastase or cathepsin G, except for cytin and therin. Furthermore, tessulin, in conjunction with other serine-protease inhibitors isolated from Theromyzon (therin, theromin), significantly diminishes the level of human granulocyte and monocyte activation induced by lipopolysaccharides (10 µg). The combined level of inhibition is higher than that of aprotinin, another serine-protease inhibitor used biomedically. Thus, tessulin may be clinically significant in reducing inflammatory events.Keywords : protease inhibitors; trypsin-chymotrypsin inhibitor.In numerous pathological processes, the crucial role played by proteases is becoming more apparent. This critical role creates a need for the development of non-toxic protease inhibitors for in vivo clinical applications. Because of the specific recognition by proteases of defined amino acid sequences, it is possible to inhibit these enzymes when they are involved in pathological processes [1]. The involvement of proteolytic enzymes in a number of degenerative diseases, e.g., pancreatitis [zymogenic forms of proteolytic enzymes (trypsin 1 and 2, chymotrypsin A [2, 3] and elastase [4])], is becoming more evident as is the need for curtailing this activity in uncalled-for situations [5Ϫ7]. In this regard, aprotinin, a 6.5-kDa trypsin and kallikrein inhibitor isolated from bovine organs [8] has been used for more than three decades as an intensive care drug for acute pancreatitis [9], demonstrating the significance of this class of enzyme.In hematophageous leeches, animals that must escape hostimmune surveillance, studies on serine-protease inhibitors have yielded significant findings relating to the clinical importance of these enzyme inhibitors. Of two groups of serine-protease [19]. However, some of these inhibitors exhibit different amino acid sequences and inhibitory activities; their three-dimensional structures share the same structural motif with the leech antihemostatic protein (L.A.P.) [20]. Interestingly, their mechanisms of action and epitopes important for binding to their respective targets are distinct as well [20], suggesting that through evolution different strategies have emerged to deal with a similar problem.Among the second group of serine-protea...

show abstract

[70] Trypsin-plasmin inhibitors (Bdellins) from leeches

Cited by 24 publications

References 8 publications

Theromin, a Novel Leech Thrombin Inhibitor

Theromin, a Novel Leech Thrombin Inhibitor

Inhibition of Fibrinolytic Enzymes by Thrombin Inhibitors

Amino‐acid‐sequence determination and biological activity of tessulin, a naturally occurring trypsin‐chymotrypsin inhibitor isolated from the leech Theromyzon tessulatum

Contact Info

Product

Resources

About