| abstract |
The present invention provides a crystallized NC1 domain hexamer of Type IV collagen, and methods for making the crystal, wherein the NC1 domain hexamer is cystallized such that the three dimensional structure of the cystallized NC1 domain hexamer can be determined to a resolution of at least 3 A or better. The present invention also provides a method for designing compounds to inhibit angiogenesis, tumor growth, tumor metastasis, endothelial cell adhesion and/or proliferation, and/or basal lamina assembly, comprising analyzing the three dimensional structure of a cystallized Type IV collagen NC1 domain hexamer produced by the methods of the invention, and identifying and synthesizing compounts that target regions of the NC1 domain that have been identified by the analysis as being important for type IV collegen heterotrimer and hexamer assembly. The present invention also provides novel polypeptides designed by the rational drug design methods of the present invention, based on an analysis of the type IV collagen NC1 hexamer structur e disclosed herein. |