Methods of designing and producing novel compounds having improved binding affinity for CD154 or other trimeric proteins

摘要

The present invention relates to methods for designing and producing novel CD40:CD154 binding interrupter compounds and methods using these compounds to treat conditions associated with inappropriate CD154 activation in a subject. This invention also relates to novel methods for screening candidate compounds for the properties of specifically binding CD154 and interrupting CD40:CD154 interaction. This invention further relates to methods of improving the binding affinity, or the ability to block CD40/CD154 interaction, of a synthetic molecule for a trimeric protein, such as CD154. These methods comprise converting a first synthetic molecule that cannot promote lattice or aggregate formation of its target trimeric protein to a second synthetic molecule that can promote lattice or aggregate formation of its target trimeric protein. This invention also relates to a two-dimensional lattice or aggregate comprising a plurality of trimeric CD154 on a cell surface or in solution, wherein the lattice or aggregate is formed by bivalent anti-CD154 antibodies associated with trimeric CD154 molecules.