The idea of antagonizing cytokines by blocking their receptors with a small molecule has been a long and difficult road. Early on (Labriola-Tompkins et al. 1991), IL-1 was shown to have a large surface area interacting with its receptor - highlighting why so many high throughput screens had failed to find a low molecular weight antagonist. Inhibitors have been found, but these are larger peptides, which can block the large surface area of the interaction (Akeson et al. 1996). More recently, examples based on rational design have been shown for TNF antagonists (He et al. 2005), based on allosteric binding modifying the structure and inhibiting function. Alternatively, binding may be designed for the 'hot spot' that corresponds to protein interfaces particularly adept at binding to proteins, peptides and thus even small molecules (Arkin and Wells 2004).
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Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.