chapter  18
14 Pages

Inhibition of Ras-Dependent Signal Transduction for Therapeutic Purposes: Protein Engineering of a Ras-Specific Guanine Nucleotide Exchange Factor

ByMarco Vanoni, Paola BossiJ., lOccardo Bertini and Lilia Alberghina

Protein engineering may aid in the development of new pharmacological lead compounds, not only by allowing the unravelling of the molecular mechanisms of pharmacologically relevant targets, but directly providing potential lead compounds to be used in clinical trials. The major advance of this approach is that it can be used rationally to design variant proteins with pharmacologically useful properties: in other words, proteins can be designed - or screened - to fulfill specific needs in order to alter a given signal transduction pathway. Thus this approach may bypass - or effectively complement - high throuput screenings by directly providing structural scaffolds to be used as basis to rationally design molecules interfering with the desired targets.