Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase

摘要

Human thymidylate synthase (hTS), an enzyme that plays a key role in DNA synthesis, is a target for several clinically important anticancer drugs. Inhibitors of hTS are widely used in chemotherapy; the best known are raltitrexed, pemetrexed, and 5-fluorouracil (1). However, their use is associated with drug resistance. Thus, compounds with different inhibitory mechanisms are required to combat resistance. We have designed peptides that specifically target the protein-protein interface in hTS, a dimeric protein composed of two identical polypeptide chains.