Stabilization of Protein-Protein Interactions in chemical biology and drug discovery.

摘要: More than 300,000 Protein-Protein Interactions (PPIs) can be found in human cells. This number is significantly larger the of single proteins, which are classical targets for pharmacological intervention. Hence, specific and potent modulation PPIs by small, drug-like molecules would tremendously enlarge "druggable genome" enabling novel ways drug discovery essentially every disease. strategy especially promising diseases with difficult like intrinsically disordered proteins or transcription factors, example neurodegeneration metabolic diseases. Whereas potential PPI has been recognized terms development inhibitors that disrupt prevent a binary protein complex, opposite (or complementary) to stabilize not yet realized systematic manner. fact rather surprising given impressive natural product examples confer their activity stabilizing PPIs. In addition, recent years more synthetic being published work as stabilizers, despite majority they initially have designed such. Here, we describe from both products well advocating stronger consideration stabilization approach chemical biology discovery.