Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc

SPECIFIC AIMSWe have reported that a retro-inverso (RI) form of helix1 (H1) of Myc linked to a RI internalization sequence inspired from the third α helix of Antennapedia (Int), RI-Int-H1-S6A,F8A, is endowed with antiproliferative and proapoptotic activity toward cancer cell lines MCF-7 and HCT-116. The activity apparently depended on the presence of the Myc motif.The aims of the present work were to 1) synthesize variant molecules of our original lead [each side chain of the D-amino acids (D-aa) was exchanged with the methyl group of an alanine; we tested two D-proline substituted molecules; we tested a longer RI-Int-H1-S6A,F8A-loop-H2 peptido-mimetic molecule]; 2) investigate the Myc/Max dimerization domain at the level of circular dichroism spectroscopy (CD) and anisotropy to understand the relationships between physicochemical effects and biological activity of our molecules; 3) analyze the structure of our peptido-mimetic molecules at the level of circular dichroism spectroscopy and nuclear magnetic ...