Sunflower Trypsin Inhibitor-1 (SFTI-1): Sowing Seeds in the Fields of Chemistry and Biology

Nature-derived cyclic peptides have proven to be a vast source of inspiration for advancing modern pharmaceutical design and synthetic chemistry. The focus of this Review is sunflower trypsin inhibitor-1 (SFTI-1), one of the smallest disulfide-bridged cyclic peptides found in nature. SFTI-1 has an unusual biosynthetic pathway that begins with a dual-purpose albumin precursor and ends with the production of a high-affinity serine protease inhibitor that rivals other inhibitors much larger in size. Investigations on the molecular basis for SFTI-1′s rigid structure and adaptable function have planted seeds for thought that have now blossomed in several different fields. Here we survey these applications to highlight the growing potential of SFTI-1 as a versatile template for engineering inhibitors, a prototypic peptide for studying inhibitory mechanisms, a stable scaffold for grafting bioactive peptides, and a model peptide for evaluating peptidomimetic motifs and platform technologies.