TY - JOUR
T1 - Peptide-Boronic Acid Inhibitors of Flaviviral Proteases: Medicinal Chemistry and Structural Biology
AU - Nitsche, Christoph
AU - Zhang, Linlin
AU - Weigel, Lena F.
AU - Schilz, Jonas
AU - Graf, Dominik
AU - Bartenschlager, Ralf
AU - Hilgenfeld, Rolf
AU - Klein, Christian D.
PY - 2017/1/12
Y1 - 2017/1/12
N2 - A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens.
AB - A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens.
UR - http://www.scopus.com/inward/record.url?scp=85018193437&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.6b01021
DO - 10.1021/acs.jmedchem.6b01021
M3 - Journal articles
C2 - 27966962
AN - SCOPUS:85018193437
SN - 0022-2623
VL - 60
SP - 511
EP - 516
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -