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KOSK-II-Katalyse og org.synt.kjemi II

Design and chemical synthesis of membrane active peptidomimetics as novel anticancer agents

Awarded: NOK 2.3 mill.

Research groups at the University of Tromsø and the University Hospital of Northern-Norway have for more than 10 years studied structure-activity relationships of membrane active anticancer peptides and have identified important structural properties for the cytotoxic effects of the peptides against certain cancer cells. Based on this knowledge we have recently developed a novel class of highly potent anticancer beta-peptidomimetics that have a higher selectivity against certain cancer cells than reported for many conventional anticancer drugs. The high potency and selectivity of the beta-peptidomimetics for cancer cells is thought to derive from their ability to form exclusive amphipathic conformations that enable specific binding to negatively charged s urface phosphatidyl serine and sialic acid on cancer cells, and killing of the cancer cells by cytoplasmic membrane depolarization or destruction of the mitochondria in cancer cells. The beta-peptidomimetics are highly potent as novel anticancer agents by being more resistant against degradation by proteolytic enzymes than membrane active anticancer peptides, which is an important property for achieving cytotoxic effects against tumours in vivo. The beta-peptidomimetics are also much shorter in size than membrane active anticancer peptides so far described in the literature, and may thereby reduce the problems associated with immunogenic responses to peptide-drugs in patients. By their presumed lytic mechanism of action the beta-peptidomimetics are not li kely to be substrates for multi-drug resistance proteins in cancer cells, which are often associated with long term use of anticancer drugs, and they may thereby provide a novel approach for treating patients with multi-resistant tumours.

Funding scheme:

KOSK-II-Katalyse og org.synt.kjemi II