“…Regardless of the particular approach, inhibitor development with small-molecule HTS approaches depends on the solubility of chemical moieties (Erlanson, 2012). This has prompted the use of phenotypic screens to initialize screening (Wagner, 2016), and is one of the driving forces behind the field of peptidomimetics, which aims to utilize favorable qualities of peptides, including aqueous solubility, membrane permeability and internalization capacity, while maintaining the ability to interact with proteins and avoiding degradation through proteolysis (Vagner, Qu, & Hruby, 2008). Peptide libraries have also been generated via solid-phase synthesis (Bessette, Rice, & Daugherty, 2004;Kenrick & Daugherty, 2010;Ryvkin et al, 2018;Sidhu, 2000), by covalently linking peptides to a resin and conducting the synthesis in the immobilized form (Fields, 2002).…”