“…Furthermore, SFTI-1 is readily tolerant of residue substitutions, exemplified by a wide range of combinatorial and rational design variants that have been applied to convert SFTI-1 into potent and stable inhibitors of therapeutically relevant proteases, including matriptases (Quimbar et al., 2013; Fittler et al., 2014; Gitlin et al., 2015), kallikreins (Shariff et al., 2014; Chen et al., 2016; de Veer et al., 2016; Jendrny and Beck-Sickinger, 2016), chymotrypsin (Swedberg et al., 2017), and furin (Fittler et al., 2015). SFTI-1 has also proven to be a useful scaffold for presenting and stabilizing small bioactive epitopes that by themselves would be unstable and not effective as pharmaceuticals (Chan et al., 2011; Qiu et al., 2017; Durek et al., 2018). These engineered cyclic SFTI-1 analogues uniformly display significantly enhanced serum stability compared with their linear counterparts, overcoming a major limitation of peptide-based therapeutics (Wang and Craik, 2018).…”