| Popis: |
Publisher Summary This chapter discusses the role of purine-binding enzymes as cancer targets. It also provides an overview of kinesin spindle protein (KSP), a member of kinesin superfamily of MT motors, which convert the energy released from ATP hydrolysis into mechanical force for transport along microtubules in the cell. The ideal target for small molecule drug discovery is one that is essential for the disease state, yet nonessential for normal tissues. One recently emerged class of drugable targets is the protein kinases, exemplified by bcr-abl, which is the target of the highly successful new CML drug, Gleevec. The common drugable feature of the kinase class is the ability to bind ATP. The ATP purine moiety is bound in a hydrophobic environment of the active site and stabilized by key hydrogen bonds. Such a site favors binding of flat, aromatic heterocycles, a class of compound that has proven amenable to optimization and drug development, thus, making kinases eminently drugable. However, kinases are not the only class of enzyme that binds purines through key hydrogen bonds and hydrophobic stacking interactions; other such purine-binding enzymes include ATPases, GTPases, sulfotransferases, etc. Thus, these enzymes offer additional possibilities for drug discovery. To illustrate the potential of this emerging class of drug targets, this chapter focuses on the oncology and specifically on ATPases, GTPases and sulfotransferases. |
