Abstract

Alterations in apoptotic pathways have been implicated in many debilitating diseases such as cancer and neurodegenerative disorders.1,2 Thus, targeting cell death pathways has always been therapeutically attractive. In particular, as it is conceptually easier to kill than to sustain cells, abundant attention has been focused on anti-cancer therapies using pro-apoptotic agents such as conventional radiation and chemo-therapy. These treatments are generally believed to trigger activation of the mitochondria-mediated apoptotic pathways. However, these therapies lack molecular specificity. Over the last year or so, the discovery and structural characterization of an IAP-binding peptide motif have generated much enthusiasm in screening for an anti-cancer drug tailored for the caspase pathways.3 Apoptosis is primarily executed by activated caspases, a family of cysteine proteases with aspartate specificity in their substrates. Caspases are produced in cells as catalytically inactive zymogens and must be proteolytically processed to become active proteases during apoptosis. In normal surviving cells that have not received an apoptotic stimulus, most caspases remain inactive. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA–ligand complexes. The predictive power of LigandRNA favorably compares to five other publicly available methods. Here, in Biogenea we have for the first time discovered an in silico designed conserved motif-like tetrapeptide consisting of high free anad total binding energy mimetic pharmastructures for the potentiating apoptosis through IAP-binding as a possible future therapeutic compound using the BiogenetoligandorolTM and the LigandRNA.