Methods of selecting compstatin mimetics
The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and/or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.
1. A method comprising steps of:
(i) providing a three-dimensional structure of C3 or a portion thereof to which compstatin binds;
(ii) computationally docking a plurality of molecular structures with the structure of C3;
(iii) selecting a molecular structure from the plurality of molecular structures that binds to substantially the same site as that to which compstatin binds;
(iv) testing the ability of a test compound having the molecular structure selected in step (iii) to bind to C3, wherein the testing comprises contacting C3 with labeled compstatin (SEQ ID NO: 8) in the presence of different concentrations of the test compound; and
(v) identifying the test compound as a compstatin mimetic if it diminishes binding of the labeled compstatin to C3 by at least 25%.
2. The method of claim 1 , wherein the test compound is identified as a candidate compstatin mimetic if it diminishes binding of the labeled compstatin to C3 by at least 50%.