摘要:
Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.
摘要:
Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1–3 and kringles 1–4.
摘要:
One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.
摘要:
The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 μg/kg/day to 20 μg/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.
摘要翻译:本发明提供重组纤溶酶原激活物抑制剂-1(PAI-1)同种型23在增加纤溶酶活性,抑制血管生成性血管舒张,促进斑块回归和治疗动脉粥样硬化的方法中的用途,其通过对需要治疗的受试者施用有效量 的重组纤溶酶原激活物抑制剂型同种型23(rPAI-123)。 在一些实施方案中,rPAI-123如SEQ ID NO:5-8所示。 在其它实施方案中,rPAI-123以约2.5μg/ kg /天至20μg/ kg /天的剂量施用。 在另外的实施方案中,有效量达到rPAI-123与PAI-1的比例在约1:2至3:1的范围内。
摘要:
The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 μg/kg/day to 20 μg/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.
摘要翻译:本发明提供重组纤溶酶原激活物抑制剂-1(PAI-1)同种型23在增加纤溶酶活性,抑制血管生成性血管舒张,促进斑块回归和治疗动脉粥样硬化的方法中的用途,其通过对需要治疗的受试者施用有效量 的重组纤溶酶原激活物抑制剂型同种型23(rPAI-123)。 在一些实施方案中,rPAI-123如SEQ ID NO:5-8所示。 在其它实施方案中,rPAI-123以约2.5μg/ kg /天至20ug / kg /天的剂量施用。 在另外的实施方案中,有效量达到rPAI-123与PAI-1的比例在约1:2至3:1的范围内。
摘要:
Recombinant plasminogen activator inhibitor-1 (PAI-1) isoforms which lack the reactive center loop and contain the complete heparin-binding domain or lack at least a portion of the heparin-binding domain are described. The rPAI-1 isoforms disclosed herein may be used to modulate angiogenesis through blocking release of VEGF from a VEGF-heparin complex. Furthermore, the rPAI-1 proteins may be used to inhibit cell proliferation and migration, induce apoptosis, and produce proteolytic fragments corresponding to angiostatin kringles 1-3 and kringles 1-4. A truncated proteolytic plasmin protein of 34 kDa is also provided.
摘要:
One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.