Protein Cooperativity and Wrapping: Two Themes in the Transformative Platform of Molecular Targeted Therapy

Abstract

In spite of the enticing promises of the post-genomic era, the pharmaceutical world appears to be in a state of disarray. Projects get routinely terminated in mid-stage clinical trials, the scarcity of new targets is ever so apparent, and successful therapeutic agents are often recalled as idiosyncratic side effects are detected in patient subpopulations. The vast and seemingly endemic problems of the pharmaceutical industry are not confined to the scientific realm but the latter has much to do with the current stagnation. Properly harvesting and ultimately exploiting the output of genomic forays to make more efficacious and safer drugs has proven to be much more difficult than originally thought. In spite of the huge output of integrative post-genomic studies, drug discovery and development remain essentially a serendipitous endeavor where high-throughput screening and toxicological studies are favored over rational molecular design. Thus, more than ever, the lead in the pharmaceutical industry depends pivotally on our ability to harness innovative high-risk research. This chapter and ultimately this book may have a place in this scenario, as we introduce fundamental discoveries in basic biomolecular-level research that hold potential to become transformative and broaden the technological base of the pharmaceutical industry.