TY - DATA T1 - Phenylalanine and Phenylglycine Analogues as Arginine Mimetics in Dengue Protease Inhibitors PY - 2015/10/08 AU - Lena F. Weigel AU - Christoph Nitsche AU - Dominik Graf AU - Ralf Bartenschlager AU - Christian D. Klein UR - https://acs.figshare.com/articles/journal_contribution/Phenylalanine_and_Phenylglycine_Analogues_as_Arginine_Mimetics_in_Dengue_Protease_Inhibitors/2123887 DO - 10.1021/acs.jmedchem.5b00612.s001 L4 - https://ndownloader.figshare.com/files/3757693 KW - Dengue Protease InhibitorsDengue virus KW - peptidic inhibitors KW - nanomolar affinities KW - peptidomimetic drugs KW - serine protease NS 2B KW - phenylglycine derivatives KW - West Nile virus KW - drug discovery KW - Arginine Mimetics KW - dengue virus protease KW - Phenylglycine Analogues KW - phenylalanine side chains N2 - Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine-mimicking groups with modulated basicity. The most promising compounds were (4-amidino)-l-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease. The type and position of the substituents on the phenylglycine and phenylalanine side chains has a significant effect on the inhibitory activity against dengue virus protease and selectivity against other proteases. In addition, the non-natural, basic amino acids described here may have relevance for the development of other peptidic and peptidomimetic drugs such as inhibitors of the blood clotting cascade. ER -