The University of Michigan researchers have recently made a groundbreaking discovery in plant biochemistry, specifically in the formation of cyclic peptides. This unique ability of plants to generate cyclic peptides holds significant promise in the field of pharmaceuticals, particularly as these molecules have the potential to bind to challenging drug targets. The study, led by researchers Lisa Mydy and Roland Kersten from the U-M College of Pharmacy, shed light on a previously unknown mechanism by which plants produce cyclic peptides. Published in the journal Nature Chemical Biology, this research marks a significant step forward in the exploration of cyclic peptides for therapeutic purposes.

Within their research, Mydy and her colleagues delved into the biosynthesis of macrocyclic peptides found in plants, which are known for their therapeutic properties. In their investigations, they identified a new plant protein fold with a novel chemistry that had never been observed before. This groundbreaking discovery has the potential to lead to the development of new drugs, with one identified cyclic peptide showing promise as an anti-cancer agent. Mydy expressed her excitement about the discovery, highlighting the rarity of such breakthroughs in scientific research.

By examining the peptide cyclase, specifically the protein AhyBURP found in peanut plant roots, the researchers uncovered a unique mechanism involving copper and oxygen. Through X-ray crystallography and the use of the Advanced Photon Source at Argonne National Laboratory, the team discovered that AhyBURP utilizes copper and oxygen in a distinct way that merits further investigation. Unlike most cyclic peptides that require additional enzymes for cyclization, AhyBURP can perform this process autonomously within the protein itself. This novel chemistry involving copper and oxygen within a protein presents a unique opportunity for future drug development.

The discovery of this new plant protein and its ability to generate cyclic peptides stems from ongoing work in Kersten’s lab, within the U-M Natural Product Discovery Initiative. By screening plant genetic sequences for genes related to new chemistry, the researchers identified cyclic peptide products and their associated proteins as potential targets for drug development. The structured and stable nature of cyclic peptides makes them promising candidates for drug design, as they can effectively bind to drug targets and remain intact within the body. Moreover, the potential use of cyclic peptides as anti-cancer agents offers hope for the development of new therapeutics to combat this deadly disease.

The research conducted by the University of Michigan researchers into the biochemistry of cyclic peptides represents a significant advancement in the field of pharmaceuticals. The discovery of a new plant protein fold with unique chemistry for cyclic peptide formation opens up new avenues for drug development and therapeutic interventions. With further exploration and understanding of this novel mechanism, there is great potential for the translation of this research into tangible benefits for human health and disease treatment. The future of drug discovery and development looks promising with the continued exploration of cyclic peptides and their applications in pharmaceuticals.

Chemistry

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