{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:30:23Z","timestamp":1790886623842,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T00:00:00Z","timestamp":1357776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A series of new substrate analogue inhibitors of the WNV NS2B\u2013NS3 protease containing decarboxylated arginine mimetics at the P1 position was developed. Among the various analogues, <jats:italic>trans<\/jats:italic>\u2010(4\u2010guanidino)cyclohexylmethylamide (GCMA) was identified as the most suitable P1 residue. In combination with dichloro\u2010substituted phenylacetyl groups at the P4 position, three inhibitors with inhibition constants of &lt;0.2\u2005\u03bc<jats:sc>M<\/jats:sc> were obtained. These GCMA inhibitors have a better selectivity profile than the previously described agmatine analogues, and possess negligible affinity for the trypsin\u2010like serine proteases thrombin, factor\u2005Xa, and matriptase. A crystal structure in complex with the WNV protease was determined for one of the most potent inhibitors, 3,4\u2010dichlorophenylacetyl\u2010Lys\u2010Lys\u2010GCMA (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>=0.13\u2005\u03bc<jats:sc>M<\/jats:sc>). The inhibitor adopts a horseshoe\u2010like conformation, most likely due to a hydrophobic contact between the P4 phenyl ring and the P1 cyclohexyl group, which is further stabilized by an intramolecular hydrogen bond between the P1 guanidino group and the P4 carbonyl oxygen atom. These inhibitors are stable, readily accessible, and have a noncovalent binding mode. Therefore, they may serve as suitable lead structures for further development.<\/jats:p>","DOI":"10.1002\/cmdc.201200497","type":"journal-article","created":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T15:57:41Z","timestamp":1357833461000},"page":"231-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Development and Characterization of New Peptidomimetic Inhibitors of the West Nile Virus NS2B\u2013NS3 Protease"],"prefix":"10.1002","volume":"8","author":[{"given":"M. Zouhir","family":"Hammamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Haase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Hammami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Hilgenfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Steinmetzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,10]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.56.012302.160654"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0704.017401"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201010"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100012"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(85)90446-5"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.10.195"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1073"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607641200"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986708786242804"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051374"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1767"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.12.003"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.12.047"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01508-07"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2012.02.003"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.05.015"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0607606"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800503y"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.07.002"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.072753207"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.11.026"},{"key":"e_1_2_6_22_2","first-page":"16","volume":"109","author":"Bajusz S.","year":"1982","journal-title":"Folia Haematol. Int. Mag. Klin. Morphol. Blutforsch."},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0960-894X(96)00442-8"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314151200"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm051272l"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.12.042"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2011996"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9012455"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.04.055"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm960762y"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1466"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm970397q"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.11.013"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.2217\/14796694.5.1.97"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1107\/S002188980802476X"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4473"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01935-1"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573406053402569"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407607101"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm300337q"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.2174\/157340606777724040"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.332643"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.3998\/ark.5550190.0011.816"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2006.11.009"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049512006395"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6316-9_4"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905036693"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(68)90205-2"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904011679"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/355472a0"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889897003907"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889800018227"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj0550170"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.03.050"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm960668h"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201200497","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201200497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:19:34Z","timestamp":1760275174000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201200497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,10]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1002\/cmdc.201200497"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201200497","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,10]]},"assertion":[{"value":"2012-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}