Bioorganic Studies on the Key Natural Products from Venomous Mammals and Marine Invertebrates

Abstract

Abstract The discovery of new bioactive molecules, facilitated by a deeper understanding of nature, will advance our knowledge of biological processes and lead to new strategies to treat disease. Recent technological advancements including spectroscopic analyses and genetic approaches have provided outstanding opportunities for new discoveries, even in the case of scarce, unstable, and composite compounds. This account summarizes two recent aspects of bioorganic chemistry: mammalian venoms and antitumor marine macrolides. Due to the interesting ecology of venomous mammals, we examined the constituents of mammalian venom, and identified unique neurotoxic peptides and kallikrein-like proteases in shrews and platypus. The present findings may lead to the development of valuable vasoactive or pain-relief agents, and to a deeper understanding of the biological evolution of vertebrates in relation to toxic substances. We have also established the target proteins and mode of actions of aplyronine A, a potent antitumor and apoptogenic marine macrolide. The complexity and diversity of actin-targeting natural products might enable them to achieve multiple interactions with as-yet-unidentified biomacromolecules, such as cytoskeleton proteins and focal adhesion proteins, which should offer better perspectives for the design and development of new antitumor drugs.