PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3)
Large efforts have been made to target integrin αVβ3 of endothelial cells. We have successfully developed a new class of protein (Ref to as ProAgio) by rational protein design using a stable host protein, domain 1 of cell adhesion protein CD2. ProAgio is designed to target integrin αVβ3 at a novel s...
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ndltd-GEORGIA-oai-scholarworks.gsu.edu-biology_diss-11992017-07-18T15:37:52Z PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) Turaga, Ravi C Large efforts have been made to target integrin αVβ3 of endothelial cells. We have successfully developed a new class of protein (Ref to as ProAgio) by rational protein design using a stable host protein, domain 1 of cell adhesion protein CD2. ProAgio is designed to target integrin αVβ3 at a novel site and induces angiogenic endothelial cell apoptosis by recruiting and activating caspase 8 to the cytoplasmic domain of the targeted integrins. Tests with tumor xenograft models show that ProAgio strongly inhibits tumor growth. Histology analyses indicate that tumor vessels are reduced, while the established vasculatures are not affected. Toxicity analyses demonstrate that ProAgio is not toxic to mouse. Our study develops an effective anti-angiogenesis agent and provides a new platform for development of therapeutics by targeting integrins. We have successfully developed an anti-angiogenesis protein targeting integrin αVβ3 at a novel site by rational protein design. The developed agent is not toxic to non-cancerous blood vessels and other tissue/organs, providing an excellent candidate for future potential clinical development. Our developed protein is one of the very few examples that do not act through targeting VEGF/VEGFR or any other RTK pathways. The βA groove is present in almost all other β integrins. This approach may be applicable to develop agents targeting the similar βA groove of other integrin pairs, which can address wide array of pathological conditions such as AMD, Rheumatoid Arthritis, Osteoporosis etc. 2017-08-08T07:00:00Z text application/pdf http://scholarworks.gsu.edu/biology_diss/189 http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1199&context=biology_diss Biology Dissertations ScholarWorks @ Georgia State University Angiogenesis Fibrosis Integrin αVβ3 integrins cirrhosis stellate cells endothelial cells |
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Angiogenesis Fibrosis Integrin αVβ3 integrins cirrhosis stellate cells endothelial cells Turaga, Ravi C PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
description |
Large efforts have been made to target integrin αVβ3 of endothelial cells. We have successfully developed a new class of protein (Ref to as ProAgio) by rational protein design using a stable host protein, domain 1 of cell adhesion protein CD2. ProAgio is designed to target integrin αVβ3 at a novel site and induces angiogenic endothelial cell apoptosis by recruiting and activating caspase 8 to the cytoplasmic domain of the targeted integrins. Tests with tumor xenograft models show that ProAgio strongly inhibits tumor growth. Histology analyses indicate that tumor vessels are reduced, while the established vasculatures are not affected. Toxicity analyses demonstrate that ProAgio is not toxic to mouse. Our study develops an effective anti-angiogenesis agent and provides a new platform for development of therapeutics by targeting integrins. We have successfully developed an anti-angiogenesis protein targeting integrin αVβ3 at a novel site by rational protein design. The developed agent is not toxic to non-cancerous blood vessels and other tissue/organs, providing an excellent candidate for future potential clinical development. Our developed protein is one of the very few examples that do not act through targeting VEGF/VEGFR or any other RTK pathways. The βA groove is present in almost all other β integrins. This approach may be applicable to develop agents targeting the similar βA groove of other integrin pairs, which can address wide array of pathological conditions such as AMD, Rheumatoid Arthritis, Osteoporosis etc. |
author |
Turaga, Ravi C |
author_facet |
Turaga, Ravi C |
author_sort |
Turaga, Ravi C |
title |
PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
title_short |
PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
title_full |
PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
title_fullStr |
PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
title_full_unstemmed |
PROAGIO (A PROTEIN DESIGNED TO TARGET INTEGRIN αVβ3) |
title_sort |
proagio (a protein designed to target integrin αvβ3) |
publisher |
ScholarWorks @ Georgia State University |
publishDate |
2017 |
url |
http://scholarworks.gsu.edu/biology_diss/189 http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1199&context=biology_diss |
work_keys_str_mv |
AT turagaravic proagioaproteindesignedtotargetintegrinavb3 |
_version_ |
1718496660044120064 |