Synthesizing fatty acids like peptides to discover functional fatty acids
Polyunsaturated fatty acids (PUFAs) constitute a pivotal group of lipids, exemplified by omega-3 fatty acids such as docosahexaenoic acid (DHA). PUFAs have attracted attention due to their various biological functions and health benefits. However, their chemical synthesis requires expert-level synthetic skills and lengthy processes, making it a significant bottleneck in research and medicinal applications.
Here, the team has overcome this bottleneck by adopting solid-phase synthesis, the most common and reliable method for peptides and nucleic acids. Solid-phase synthesis is highly useful in bio-related chemistry fields, such as combinatorial chemistry, which requires a facile and parallel synthetic approach. However, this method has traditionally been limited to biopolymers (or oligomers), including peptides and nucleic acids. The team has developed a fully solid-phase synthesis method that enables the rapid and precise synthesis of PUFAs.
Additionally, a novel anti-inflammatory fatty acid, Antiefin, has been discovered from a PUFA library constructed using the developed method. This achievement is expected to contribute to the elucidation of biological phenomena and disease mechanisms related to PUFAs, the advancement of data-driven life sciences, and the development of lipid-based pharmaceuticals.
Papers
Journal: Nature Chemistry
Title: Expedited access to polyunsaturated fatty acids and biofunctional analogs by full solid-phase synthesis
Authors: Yutaro Saito*, Mayuko Akita, Azusa Saika, Yusuke Sano, Masashi Hotta, Jumpei Morimoto, Akiharu Uwamizu, Junken Aoki, Takahiro Nagatake, Jun Kunisawa*, Shinsuke Sando*