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KMID : 0624620110440010034
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BMB Reports
2011 Volume.44 No. 1 p.34 ~ p.39
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A novel variant of t-PA resistant to plasminogen activator inhibitor-1; expression in CHO cells based on In Silico experiments
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Davami Fatemeh
Sardari Soroush
Majidzadeh-A Keivan
Hemayatkar Mahdi
Barkhordari Farzaneh
Enayati Somayeh
Adeli Ahmad
Mahboudi Fereidoun
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Abstract
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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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KEYWORD
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Amidolytic activity, Chinese hamster ovary (CHO), In Silico, Plasminogen activator inhibitor-1 (PAI-1), Tissue plasminogen activator (t-PA)
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