Review seed biopharmaceutical cyclic peptides: From discovery to applications

Mini-proteins (or peptides) with disulfide bond/s and a cyclic backbone offer exciting opportunities for applications in medicine, as these ribosomally synthesized and posttranslationally modified peptides are exceptionally stable and amenable to grafting epitopes with desirable activities. Here I discuss important aspects of the discovery and applications of disulfide-bonded cyclic peptides from seeds, i.e., the trypsin inhibitor cyclotides and the preproalbumin with sunflower trypsin inhibitor-derived peptides, focusing on bioanalytical methods for and insights generated from their discovery as well as their potential use as engineering scaffolds for peptide-based drug design. The recent discovery of their precursors and processing enzymes could potentially enable in planta production of designer disulfide-bonded cyclic peptides, preferably in edible seeds, and address the demand for new biopharmaceutical peptides in a cost-effective manner.