Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2012.11.008
Title: Exploring the binding of peptidic West Nile virus NS2B-NS3 protease inhibitors by NMR
Authors: Kang, C.
Gayen, S.
Wang, W.
Severin, R.
Chen, A.S.
Lim, H.A.
Chia, C.S.B.
Schüller, A. 
Doan, D.N.P.
Poulsen, A.
Hill, J.
Vasudevan, S.G. 
Keller, T.H.
Keywords: Induced fit
NMR study
Peptide inhibitors
WNV protease
Issue Date: Feb-2013
Source: Kang, C., Gayen, S., Wang, W., Severin, R., Chen, A.S., Lim, H.A., Chia, C.S.B., Schüller, A., Doan, D.N.P., Poulsen, A., Hill, J., Vasudevan, S.G., Keller, T.H. (2013-02). Exploring the binding of peptidic West Nile virus NS2B-NS3 protease inhibitors by NMR. Antiviral Research 97 (2) : 137-144. ScholarBank@NUS Repository. https://doi.org/10.1016/j.antiviral.2012.11.008
Abstract: West Nile virus (WNV) NS2B-NS3 protease is an important drug target since it is an essential protein for the replication of the virus. In order to determine the minimum pharmacophore for protease inhibition, a series of dipeptide aldehydes were synthesized. The 50% inhibitory concentration (IC50) measurements revealed that a simple acetyl-KR-aldehyde was only threefold less active than 4-phenyl-phenylacetyl-KKR-aldehyde (1) (Stoermer et al., 2008) that was used as the reference compound. The ligand efficiency of 0.40kcal/mol/HA (HA=heavy atom) for acetyl-KR-aldehyde is much improved compared to the reference compound 1 (0.23kcal/mol/HA). The binding of the inhibitors was examined using 1H-15N-HSQC experiments and differential chemical shifts were used to map the ligand binding sites. The biophysical studies show that the conformational mobility of WNV protease has a major impact on the design of novel inhibitors, since the protein conformation changes profoundly depending on the structure of the bound ligand. © 2012 Elsevier B.V.
Source Title: Antiviral Research
URI: http://scholarbank.nus.edu.sg/handle/10635/110074
ISSN: 01663542
DOI: 10.1016/j.antiviral.2012.11.008
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