On The Cover

Computer modeling of peptidomimetic ISS 610 and native Stat3 phosphopeptide bound to the SH2 pocket of Stat3. This illustration compares the predicted lowest energy GOLD docked conformation of the Stat3 inhibitor peptidomimetic, ISS 610 (green), to the COOH-terminal phosphotyrosine peptide (AAPY*LK, orange) of the associated Stat3 monomer in the SH2 domain of Stat3 (pale blue) determined from the crystal structure. By having access to hydrophobic and hydrogen bonding interactions on the protein surface, which are otherwise not accessible to the native phosphopeptide seequence, ISS 610 disrupts Stat3 dimerization. Thus, ISS 610 inhibits Stat3 signaling and biological functions, and induces apoptosis of oncogenically transformed cells. For details, see Turkson et al. in this issue.