Targeted lytic peptides - a new class of molecules designed for lysis of mitochondria in tumor cells

Despite monumental efforts in finding and developing cures, cancer is still a common and life threatening disease; one in three will get cancer and one in five will die of it. Lytix Biopharma AS is developing drugs for treatment of cancer and infection based on lytic peptides and peptidomimetics. The anti-tumor peptides are selective against cancer cells and work by lysing the cancerous cell membranes. Local treatment of solid tumors with this mechanism of action also seems to trigger inflammatory respo nses that work like an endogenous vaccination against the tumor. We have seen that these lytic effector molecules can be combined with molecular elements that target cancer cells and inhibit tumor growth systemically. The antiinfective drug candidates a re small and non-toxic against our cells as they do not lyse nor cross the cell membranes. SAMP?s can however be designed to also lyse mitochondrial cell membranes and thus kill eukaryotic cells if they can be transported over the cell membrane. In this proposal we suggest to explore linking very small and specially designed SAMP lytic effector molecules with molecules that targets and penetrates cancer cell membranes. In this manner the generally non-toxic SAMP molecules will be translocated over the c ell membranes, enter the interior of the cells where they will lyse the inner mitochondrial membrane and thus cause cell death. The targetor part of the molecules will be designed in a way that makes them particularly effective against cancer cells. The c ombined molecule will thus have three distinct parts; an effector that will lyse the mitrochondrial inner cell membrane, a targetor that will seek up cancer cells and deliver the effector on the inside of the cell membrane and a linker that will connect t he effector and the targetor. The proposal focuses on the preparation and medicinal chemistry of effectors, linkers and targetors. Furthermore effective assay systems that part of the molecules will be developed.