Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors
[Display omitted] A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehy...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2018-07, Vol.28 (12), p.2165-2170 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2170 |
|---|---|
| container_issue | 12 |
| container_start_page | 2165 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 28 |
| creator | Amblard, Franck Zhou, Shaoman Liu, Peng Yoon, Jack Cox, Bryan Muzzarelli, Kendall Kuiper, Benjamin D. Kovari, Ladislau C. Schinazi, Raymond F. |
| description | [Display omitted]
A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition. Of the six that were synthesized and tested, compounds 42, 43, and 45 potently inhibited the protease in biochemical assay and GI-1 norovirus replicon in the nanomolar range. |
| doi_str_mv | 10.1016/j.bmcl.2018.05.012 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6425952</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0960894X18304013</els_id><sourcerecordid>S0960894X18304013</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-76929a2d130310b018b95ee7c0e26b6c0a6f32f4f32a6352e3e3a07ec6f2ca2d3</originalsourceid><addsrcrecordid>eNp9kMFq3DAQhkVpSTZpXyCH4hewM5IlOYZSKCFtA4Ec2kIPBSHL4-wstmUkrSFvXy2bhuaSw8wcZr5_-H_GLjhUHLi-3FXd5MZKAL-qQFXAxRu24VLLspag3rINtBrKq1b-PmVnMe4AuAQpT9ipaJumzbVhf348zmmLkWJh5z5XopWCHQtc7bi3ifxc-KGY_YpjseCSqPcTTZjIZSLmRfAZ2MdiCT6hjVjQvKWOkg_xPXs32DHih6d5zn59vfl5_b28u_92e_3lrnRSqVQ2uhWtFT2voebQZTtdqxAbByh0px1YPdRikLlZXSuBNdYWGnR6EC5z9Tn7fNRd9t2EvcM5ZQtmCTTZ8Gi8JfNyM9PWPPjVaClUq0QWEEcBF3yMAYdnloM5ZG125pC1OWRtQJmcdYY-_v_1GfkXbj74dDzA7H0lDCY6wtlhTwFdMr2n1_T_Ah6jlFU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Amblard, Franck ; Zhou, Shaoman ; Liu, Peng ; Yoon, Jack ; Cox, Bryan ; Muzzarelli, Kendall ; Kuiper, Benjamin D. ; Kovari, Ladislau C. ; Schinazi, Raymond F.</creator><creatorcontrib>Amblard, Franck ; Zhou, Shaoman ; Liu, Peng ; Yoon, Jack ; Cox, Bryan ; Muzzarelli, Kendall ; Kuiper, Benjamin D. ; Kovari, Ladislau C. ; Schinazi, Raymond F.</creatorcontrib><description>[Display omitted]
A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition. Of the six that were synthesized and tested, compounds 42, 43, and 45 potently inhibited the protease in biochemical assay and GI-1 norovirus replicon in the nanomolar range.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2018.05.012</identifier><identifier>PMID: 29779977</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antiviral ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Cell Line ; Cell Survival - drug effects ; Chlorocebus aethiops ; Dose-Response Relationship, Drug ; Humans ; Microbial Sensitivity Tests ; Molecular Structure ; Norovirus ; Norovirus - drug effects ; Norovirus - enzymology ; Peptide ; Peptide Hydrolases - metabolism ; Peptidomimetics - chemical synthesis ; Peptidomimetics - chemistry ; Peptidomimetics - pharmacology ; Protease inhibitor ; Protease Inhibitors - chemical synthesis ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacology ; Structure-Activity Relationship ; Vero Cells ; Virus Replication - drug effects</subject><ispartof>Bioorganic & medicinal chemistry letters, 2018-07, Vol.28 (12), p.2165-2170</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-76929a2d130310b018b95ee7c0e26b6c0a6f32f4f32a6352e3e3a07ec6f2ca2d3</citedby><cites>FETCH-LOGICAL-c455t-76929a2d130310b018b95ee7c0e26b6c0a6f32f4f32a6352e3e3a07ec6f2ca2d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2018.05.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29779977$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Amblard, Franck</creatorcontrib><creatorcontrib>Zhou, Shaoman</creatorcontrib><creatorcontrib>Liu, Peng</creatorcontrib><creatorcontrib>Yoon, Jack</creatorcontrib><creatorcontrib>Cox, Bryan</creatorcontrib><creatorcontrib>Muzzarelli, Kendall</creatorcontrib><creatorcontrib>Kuiper, Benjamin D.</creatorcontrib><creatorcontrib>Kovari, Ladislau C.</creatorcontrib><creatorcontrib>Schinazi, Raymond F.</creatorcontrib><title>Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition. Of the six that were synthesized and tested, compounds 42, 43, and 45 potently inhibited the protease in biochemical assay and GI-1 norovirus replicon in the nanomolar range.</description><subject>Animals</subject><subject>Antiviral</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Chlorocebus aethiops</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Structure</subject><subject>Norovirus</subject><subject>Norovirus - drug effects</subject><subject>Norovirus - enzymology</subject><subject>Peptide</subject><subject>Peptide Hydrolases - metabolism</subject><subject>Peptidomimetics - chemical synthesis</subject><subject>Peptidomimetics - chemistry</subject><subject>Peptidomimetics - pharmacology</subject><subject>Protease inhibitor</subject><subject>Protease Inhibitors - chemical synthesis</subject><subject>Protease Inhibitors - chemistry</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Vero Cells</subject><subject>Virus Replication - drug effects</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFq3DAQhkVpSTZpXyCH4hewM5IlOYZSKCFtA4Ec2kIPBSHL4-wstmUkrSFvXy2bhuaSw8wcZr5_-H_GLjhUHLi-3FXd5MZKAL-qQFXAxRu24VLLspag3rINtBrKq1b-PmVnMe4AuAQpT9ipaJumzbVhf348zmmLkWJh5z5XopWCHQtc7bi3ifxc-KGY_YpjseCSqPcTTZjIZSLmRfAZ2MdiCT6hjVjQvKWOkg_xPXs32DHih6d5zn59vfl5_b28u_92e_3lrnRSqVQ2uhWtFT2voebQZTtdqxAbByh0px1YPdRikLlZXSuBNdYWGnR6EC5z9Tn7fNRd9t2EvcM5ZQtmCTTZ8Gi8JfNyM9PWPPjVaClUq0QWEEcBF3yMAYdnloM5ZG125pC1OWRtQJmcdYY-_v_1GfkXbj74dDzA7H0lDCY6wtlhTwFdMr2n1_T_Ah6jlFU</recordid><startdate>20180701</startdate><enddate>20180701</enddate><creator>Amblard, Franck</creator><creator>Zhou, Shaoman</creator><creator>Liu, Peng</creator><creator>Yoon, Jack</creator><creator>Cox, Bryan</creator><creator>Muzzarelli, Kendall</creator><creator>Kuiper, Benjamin D.</creator><creator>Kovari, Ladislau C.</creator><creator>Schinazi, Raymond F.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20180701</creationdate><title>Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors</title><author>Amblard, Franck ; Zhou, Shaoman ; Liu, Peng ; Yoon, Jack ; Cox, Bryan ; Muzzarelli, Kendall ; Kuiper, Benjamin D. ; Kovari, Ladislau C. ; Schinazi, Raymond F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-76929a2d130310b018b95ee7c0e26b6c0a6f32f4f32a6352e3e3a07ec6f2ca2d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antiviral</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Chlorocebus aethiops</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Structure</topic><topic>Norovirus</topic><topic>Norovirus - drug effects</topic><topic>Norovirus - enzymology</topic><topic>Peptide</topic><topic>Peptide Hydrolases - metabolism</topic><topic>Peptidomimetics - chemical synthesis</topic><topic>Peptidomimetics - chemistry</topic><topic>Peptidomimetics - pharmacology</topic><topic>Protease inhibitor</topic><topic>Protease Inhibitors - chemical synthesis</topic><topic>Protease Inhibitors - chemistry</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Vero Cells</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Amblard, Franck</creatorcontrib><creatorcontrib>Zhou, Shaoman</creatorcontrib><creatorcontrib>Liu, Peng</creatorcontrib><creatorcontrib>Yoon, Jack</creatorcontrib><creatorcontrib>Cox, Bryan</creatorcontrib><creatorcontrib>Muzzarelli, Kendall</creatorcontrib><creatorcontrib>Kuiper, Benjamin D.</creatorcontrib><creatorcontrib>Kovari, Ladislau C.</creatorcontrib><creatorcontrib>Schinazi, Raymond F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amblard, Franck</au><au>Zhou, Shaoman</au><au>Liu, Peng</au><au>Yoon, Jack</au><au>Cox, Bryan</au><au>Muzzarelli, Kendall</au><au>Kuiper, Benjamin D.</au><au>Kovari, Ladislau C.</au><au>Schinazi, Raymond F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2018-07-01</date><risdate>2018</risdate><volume>28</volume><issue>12</issue><spage>2165</spage><epage>2170</epage><pages>2165-2170</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition. Of the six that were synthesized and tested, compounds 42, 43, and 45 potently inhibited the protease in biochemical assay and GI-1 norovirus replicon in the nanomolar range.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29779977</pmid><doi>10.1016/j.bmcl.2018.05.012</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2018-07, Vol.28 (12), p.2165-2170 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6425952 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antiviral Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Cell Line Cell Survival - drug effects Chlorocebus aethiops Dose-Response Relationship, Drug Humans Microbial Sensitivity Tests Molecular Structure Norovirus Norovirus - drug effects Norovirus - enzymology Peptide Peptide Hydrolases - metabolism Peptidomimetics - chemical synthesis Peptidomimetics - chemistry Peptidomimetics - pharmacology Protease inhibitor Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Structure-Activity Relationship Vero Cells Virus Replication - drug effects |
| title | Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T23%3A16%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis%20and%20antiviral%20evaluation%20of%20novel%20peptidomimetics%20as%20norovirus%20protease%20inhibitors&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry%20letters&rft.au=Amblard,%20Franck&rft.date=2018-07-01&rft.volume=28&rft.issue=12&rft.spage=2165&rft.epage=2170&rft.pages=2165-2170&rft.issn=0960-894X&rft.eissn=1464-3405&rft_id=info:doi/10.1016/j.bmcl.2018.05.012&rft_dat=%3Celsevier_pubme%3ES0960894X18304013%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/29779977&rft_els_id=S0960894X18304013&rfr_iscdi=true |