A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

Filippovich, I., Sorokina, N., Masci, P. P., de Jersey, J., Whitaker, A. N., Winzor, D. J., Gaffney, P. J. and Lavin, M. F. (2002) A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties. British Journal of Haematology, 119 2: 376-384. doi:10.1046/j.1365-2141.2002.03878.x


Author Filippovich, I.
Sorokina, N.
Masci, P. P.
de Jersey, J.
Whitaker, A. N.
Winzor, D. J.
Gaffney, P. J.
Lavin, M. F.
Title A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties
Journal name British Journal of Haematology   Check publisher's open access policy
ISSN 0007-1048
Publication date 2002-01-01
Sub-type Article (original research)
DOI 10.1046/j.1365-2141.2002.03878.x
Volume 119
Issue 2
Start page 376
End page 384
Total pages 9
Editor M. Greaves
Place of publication Oxford
Publisher Blackwell Publishing Ltd
Collection year 2002
Language eng
Subject C1
730103 Blood disorders
321008 Haematology
Abstract Two peptides, textilinins 1 and 2, isolated from the venom of the Australian common brown snake, Pseudonaja textilis textilis, are effective in preventing blood loss. To further investigate the potential of textilinins as anti-haemorrhagic agents, we cloned cDNAs encoding these proteins. The isolated full-length cDNA (430 bp in size) was shown to code for a 59 amino acid protein, corresponding in size to the native peptide, plus an additional 24 amino acid propeptide. Six such cDNAs were identified, differing in nucleotide sequence in the coding region but with an identical propeptide. All six sequences predicted peptides containing six conserved cysteines common to Kunitz-type serine protease inhibitors. When expressed as glutathione S-transferase (GST) fusion proteins and released by cleavage with thrombin, only those peptides corresponding to textilinin 1 and 2 were active in inhibiting plasmin with K-i values similar to those of their native counterparts and in binding to plasmin less tightly than aprotinin by two orders of magnitude. Similarly, in the mouse tail vein blood loss model only recombinant textilinin 1 and 2 were effective in reducing blood loss. These recombinant textilinins have potential as therapeutic agents for reducing blood loss in humans, obviating the need for reliance on aprotinin, a bovine product with possible risk of transmissible disease, and compromising the fibrinolytic system in a less irreversible manner.
Keyword Hematology
Recombinant Textilinin
Gene Cloning
Antihaemorrhagic Properties
Epsilon-aminocaproic Acid
Snake Pseudonaja-textilis
Common Brown Snake
Cardiopulmonary Bypass
Cardiac-surgery
Blood-loss
Myocardial Revascularization
Prothrombin Activator
Tranexamic Acid
Aprotinin
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Science Publications
Excellence in Research Australia (ERA) - Collection
 
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Created: Wed, 15 Aug 2007, 04:47:53 EST