Non Nucleic Acid Inhibitors of Protein-DNA Interactions Identified through Combinatorial Chemistry

摘要

The autoimmune disease systemic lupus erythematosus (SLE) afflicts at least 500 000 Americans, significantly shortening their life expectancy. Women are affected in 90% of cases and African Americans are several times more likely to develop the disease than Caucasians. Antibodies that bind single- and double-stranded DNA (ssDNA and dsDNA, respectively) are present in the serum of lupus patients. A subset of these antibodies are also pathogenic: they mediate a complement-dependent inflammatory response in kidney tissue (glomerulo-nephritis) often resulting in renal damage. Nonspecific im-munosupressive and cytotoxic agents can curtail glomerulo-nephritis in some patients; yet, in others they are ineffective and side effects often force discontinuation of treatment. A clear need exists for specific, broadly effective, and better tolerated therapeutics.