10.1021/acs.jmedchem.5b00612.s001
Lena F. Weigel
Lena F.
Weigel
Christoph Nitsche
Christoph
Nitsche
Dominik Graf
Dominik
Graf
Ralf Bartenschlager
Ralf
Bartenschlager
Christian D. Klein
Christian D.
Klein
Phenylalanine and
Phenylglycine Analogues as Arginine
Mimetics in Dengue Protease Inhibitors
American Chemical Society
2015
Dengue Protease InhibitorsDengue virus
peptidic inhibitors
nanomolar affinities
peptidomimetic drugs
serine protease NS 2B
phenylglycine derivatives
West Nile virus
drug discovery
Arginine Mimetics
dengue virus protease
Phenylglycine Analogues
phenylalanine side chains
2015-10-08 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Phenylalanine_and_Phenylglycine_Analogues_as_Arginine_Mimetics_in_Dengue_Protease_Inhibitors/2123887
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.