Modified plasminogen activator inhibitor type-1 and methods based thereon
a technology of activator inhibitor and plasminogen, which is applied in the direction of peptide/protein ingredients, extracellular fluid disorder, peptide sources, etc., can solve the problems of pai-1 spontaneous reverse to its latent form, most known upa inhibitors are unstable, weak or toxic in humans, etc., to reduce the enzymatic activity of pai-1, increase the half-life of the active form, and reduce the enzymatic activity
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[0042]The present invention relates to novel modified PAI-1 proteins and functionally active fragments, derivatives and analogs thereof (“modified PAI-1 molecules of the invention”), nucleic acid molecules encoding modified PAI-1 proteins molecules as well as therapeutic and prophylactic methods using modified PAI-1 molecules of the invention. The present inventors have designed and made modified PAI-1 molecules that have mutations (preferably amino acid substitutions) in or close to the (3-sheet of PAI-1 which increase the bioactivity of PAI-1, in particular, to increase the half-life of the PAI-1 active form in circulation. The invention provides modified PAI-1 molecules in which two or more amino acid residues that do not contain a sulfhydryl group have been replaced with amino acid residues that contain sulfhydryl groups such as, but not limited to, cysteine residues, so that these sulfhydryl containing residues form one or more intrachain disulfide bonds, which modified PAI-1 m...
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