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Article Dans Une Revue BMB Rep Année : 2011

A novel variant of t-PA resistant to plasminogen activator inhibitor-1; expression in CHO cells based on in silico experiments.

Résumé

Resistance to PAI-1 is a factor which confers clinical benefits in thrombolytic therapy. The only US FDA approved PAI-1 resistant drug is Tenecteplase®. Deletion variants of t-PA have the advantage of fewer disulfide bonds in addition to higher plasma half lives. A new variant was developed by deletion of the first three domains in t-PA in addition to substitution of KHRR 128-131 amino acids with AAAA in truncated t-PA. The specific activity of this new variant, 570 IU/μg, was found to be similar to those found in full length t-PA (Alteplase®), 580 IU/μg. A 65% and 85% residual activity after inhibition by rPAI-1 was observed for full length and truncated-mutant form, respectively. This new variant as the first PAI-1 resistant truncated t-PA may offer more advantages in clinical conditions in which high PAI-1 levels makes the thrombolytic system prone to re-occlusion.
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Dates et versions

pasteur-00753196 , version 1 (18-11-2012)

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Fatemeh Davami, Soroush Sardari, Keivan Majidzadeh-A, Mahdi Hemayatkar, Farzaneh Barkhordari, et al.. A novel variant of t-PA resistant to plasminogen activator inhibitor-1; expression in CHO cells based on in silico experiments.. BMB Rep, 2011, 44 (1), pp.34-9. ⟨10.5483/BMBRep.2011.44.1.34⟩. ⟨pasteur-00753196⟩

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