Compositions and methods for promoting or inhibiting angiogenesis

A method of inhibiting angiogenesis, comprising administering to a patient in need of treatment thereof an effective, angiogenesis inhibiting amount of an angiostatin agonist, angiostatin partial agonist or angiostatin allosteric promoter.

A method of promoting angiogenesis, comprising administering to a patient in need of treatment thereof an effective, angiogenesis-promoting amount of an angiostatin antagonist or an angiostatin allosteric inhibitor.

A method of screening a test compound for its ability to inhibit or enhance the binding of angiostatin to ATP synthase comprising:

• i) contacting the test compound and angiostatin with the alpha and/or beta subunits of ATP synthase under conditions such that angiostatin can bind to the subunits in the absence of the test compound, and
• ii) determining the amount of angiostatin bound to the subunits, and comparing that amount to an amount of angiostatin bound to the subunits in the absence of the test compound, wherein a reduction in the amount of angiostatin bound to the alpha and/or beta subunits of ATP synthase in the presence of the test compound indicates that the test compound inhibits the binding of angiostatin to the subunits, and wherein an increase of the amount of angiostatin bound to the alpha and/or beta subunits of ATP synthase in the presence of the test compound indicates that the test compound enhances the binding of angiostatin to the subunits.

A method of screening a test compound for its ability to modulate a bioactivity resulting from binding of angiostatin to the alpha and/or beta subunits of ATP synthase comprising:

• i) contacting the test compound and angiostatin with a cell that expresses the alpha and/or beta subunits of ATP synthase under conditions such that angiostatin can bind to the subunits in the absence of the test compound, and
• ii) determining the amount of angiostatin required to achieve the same bioactivity in the presence of the test compound as in the absence of the test compound, wherein a reduction in the amount of angiostatin required to achieve the same bioactivity in the presence of the test compound indicates that the test compound is an angiostatin agonist, partial agonist or allosteric inhibitor, and wherein an increase in the amount of angiostatin required to achieve the same bioactivity in the presence of the test compound indicates that the test compound is an angiostatin antagonist or allosteric promoter.

An expression construct comprising a vector and a nucleic acid sequence encoding the alpha and/or beta subunits of ATP synthase, operably linked to a promoter.

A monoclonal antibody or antibody fragment thereof specific for the alpha and/or beta subunits of ATP synthase that functions as an angiostatin agonist.

A monoclonal antibody or antibody fragment thereof specific for the alpha and/or beta subunits of ATP synthase that functions as an angiostatin partial agonist.

A monoclonal antibody or antibody fragment thereof specific for the alpha and/or beta subunits of ATP synthase that functions as an angiostatin inverse agonist.

A monoclonal antibody or antibody fragment thereof specific for the alpha and/or beta subunits of ATP synthase that functions as an angiostatin antagonist.

A monoclonal antibody or antibody fragment thereof specific for the alpha and/or beta subunits of ATP synthase that functions as an angiostatin allosteric modulator.