Please use this identifier to cite or link to this item: https://doi.org/10.3109/14756366.2015.1018245
Title: Peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3C protease: A P2-P4 study
Authors: Ang, MJY
Lau, QY
NG FUI MEE 
Then, SW
ANDERS POULSEN 
Cheong, YK
Ngoh, ZX
Tan, YW
Peng, J
Keller, Thomas H
HILL, JEFFREY 
CHU JANG HANN 
Brian Chia, CS
Keywords: 3C protease
EV71
Rupintrivir
peptide-based inhibitor
Antiviral Agents
Chemistry Techniques, Synthetic
Crystallography, X-Ray
Cysteine Endopeptidases
Enterovirus A, Human
Inhibitory Concentration 50
Isoxazoles
Peptidomimetics
Protease Inhibitors
Pyrrolidinones
Structure-Activity Relationship
Viral Proteins
Issue Date: 3-Mar-2016
Publisher: Informa UK Limited
Citation: Ang, MJY, Lau, QY, NG FUI MEE, Then, SW, ANDERS POULSEN, Cheong, YK, Ngoh, ZX, Tan, YW, Peng, J, Keller, Thomas H, HILL, JEFFREY, CHU JANG HANN, Brian Chia, CS (2016-03-03). Peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3C protease: A P2-P4 study. Journal of Enzyme Inhibition and Medicinal Chemistry 31 (2) : 332-339. ScholarBank@NUS Repository. https://doi.org/10.3109/14756366.2015.1018245
Abstract: © 2015 Informa UK Ltd. Enterovirus 71 (EV71) is a highly infectious pathogen primarily responsible for Hand, Foot, and Mouth Disease, particularly among children. Currently, no approved antiviral drug has been developed against this disease. The EV71 3C protease is deemed an attractive drug target due to its crucial role in viral polyprotein processing. Rupintrivir, a peptide-based inhibitor originally developed to target the human rhinovirus 3C protease, was found to inhibit the EV71 3C protease. In this communication, we report the inhibitory activities of 30 Rupintrivir analogs against the EV71 3C protease. The most potent inhibitor, containing a P2 ring-constrained phenylalanine analog (compound 9), was found to be two-fold more potent than Rupintrivir (IC50 value 3.4 ± 0.4 versus 7.3 ± 0.8 M). Our findings suggest that employing geometrically constrained residues in peptide-based protease inhibitors can potentially enhance their inhibitory activities.
Source Title: Journal of Enzyme Inhibition and Medicinal Chemistry
URI: https://scholarbank.nus.edu.sg/handle/10635/170681
ISSN: 1475-6366
1475-6374
DOI: 10.3109/14756366.2015.1018245
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