Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists
[Display omitted] Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex viv...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2015-09, Vol.23 (17), p.5846-5855 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5855 |
|---|---|
| container_issue | 17 |
| container_start_page | 5846 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 23 |
| creator | Nalla, Naresh Pallavi, Preethi Reddy, Bonam Srinivasa Miryala, Sreekanth Naveen Kumar, V. Mahboob, Mohammed Halmuthur, M. Sampath Kumar |
| description | [Display omitted]
Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate–Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant. |
| doi_str_mv | 10.1016/j.bmc.2015.06.070 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmed_primary_26234903</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089615005647</els_id><sourcerecordid>S0968089615005647</sourcerecordid><originalsourceid>FETCH-LOGICAL-e178t-7cd38a6b5d1a190046653a3288abee88fddb073d2c9aa58867c6569e0951c5ee3</originalsourceid><addsrcrecordid>eNo1kN9K5DAUxoO46Kz6AN5IHmDaPWnaNMErGf_swoAieh1OkzNjhraRpiPM4oXvsG_ok1jRvTofh-_7-PgxdiogFyDUr03edC4vQFQ5qBxq2GMzUaoyk9KIfTYDo3QG2qhD9jOlDQAUpREH7LBQhSwNyBl7vaQU1v2cp10_Pk06cew9D1237WMb18Fhy-kF2y2OIfY8rriYF3OZjUPAv7GlbKQpN5DnDocmPu38gCO9v_27w04udom72G-26-k3NSf-sLwvOK5jH9KYjtmPFbaJTr7vEXu8vnpY_M6Wtzd_FhfLjEStx6x2XmpUTeUFCgNQKlVJlIXW2BBpvfK-gVr6whnESmtVO1UpQ2Aq4SoiecTOvnqft01H3j4PocNhZ_9jmAznXwaaVrwEGmxygXpHPgzkRutjsALsJ3S7sRN0-wndgrITdPkBZol2aA</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Nalla, Naresh ; Pallavi, Preethi ; Reddy, Bonam Srinivasa ; Miryala, Sreekanth ; Naveen Kumar, V. ; Mahboob, Mohammed ; Halmuthur, M. Sampath Kumar</creator><creatorcontrib>Nalla, Naresh ; Pallavi, Preethi ; Reddy, Bonam Srinivasa ; Miryala, Sreekanth ; Naveen Kumar, V. ; Mahboob, Mohammed ; Halmuthur, M. Sampath Kumar</creatorcontrib><description>[Display omitted]
Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate–Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2015.06.070</identifier><identifier>PMID: 26234903</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adjuvants ; Carbohydrate ; Click chemistry ; Cytokines ; Drug Design ; Lipoproteins - metabolism ; Pam3Cys ; Peptides ; Toll-Like Receptor 2 - genetics ; Toll-Like Receptor 2 - metabolism ; Triazoles - chemical synthesis ; Triazoles - chemistry</subject><ispartof>Bioorganic & medicinal chemistry, 2015-09, Vol.23 (17), p.5846-5855</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2015.06.070$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26234903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nalla, Naresh</creatorcontrib><creatorcontrib>Pallavi, Preethi</creatorcontrib><creatorcontrib>Reddy, Bonam Srinivasa</creatorcontrib><creatorcontrib>Miryala, Sreekanth</creatorcontrib><creatorcontrib>Naveen Kumar, V.</creatorcontrib><creatorcontrib>Mahboob, Mohammed</creatorcontrib><creatorcontrib>Halmuthur, M. Sampath Kumar</creatorcontrib><title>Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate–Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.</description><subject>Adjuvants</subject><subject>Carbohydrate</subject><subject>Click chemistry</subject><subject>Cytokines</subject><subject>Drug Design</subject><subject>Lipoproteins - metabolism</subject><subject>Pam3Cys</subject><subject>Peptides</subject><subject>Toll-Like Receptor 2 - genetics</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Triazoles - chemical synthesis</subject><subject>Triazoles - chemistry</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kN9K5DAUxoO46Kz6AN5IHmDaPWnaNMErGf_swoAieh1OkzNjhraRpiPM4oXvsG_ok1jRvTofh-_7-PgxdiogFyDUr03edC4vQFQ5qBxq2GMzUaoyk9KIfTYDo3QG2qhD9jOlDQAUpREH7LBQhSwNyBl7vaQU1v2cp10_Pk06cew9D1237WMb18Fhy-kF2y2OIfY8rriYF3OZjUPAv7GlbKQpN5DnDocmPu38gCO9v_27w04udom72G-26-k3NSf-sLwvOK5jH9KYjtmPFbaJTr7vEXu8vnpY_M6Wtzd_FhfLjEStx6x2XmpUTeUFCgNQKlVJlIXW2BBpvfK-gVr6whnESmtVO1UpQ2Aq4SoiecTOvnqft01H3j4PocNhZ_9jmAznXwaaVrwEGmxygXpHPgzkRutjsALsJ3S7sRN0-wndgrITdPkBZol2aA</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Nalla, Naresh</creator><creator>Pallavi, Preethi</creator><creator>Reddy, Bonam Srinivasa</creator><creator>Miryala, Sreekanth</creator><creator>Naveen Kumar, V.</creator><creator>Mahboob, Mohammed</creator><creator>Halmuthur, M. Sampath Kumar</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20150901</creationdate><title>Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists</title><author>Nalla, Naresh ; Pallavi, Preethi ; Reddy, Bonam Srinivasa ; Miryala, Sreekanth ; Naveen Kumar, V. ; Mahboob, Mohammed ; Halmuthur, M. Sampath Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e178t-7cd38a6b5d1a190046653a3288abee88fddb073d2c9aa58867c6569e0951c5ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adjuvants</topic><topic>Carbohydrate</topic><topic>Click chemistry</topic><topic>Cytokines</topic><topic>Drug Design</topic><topic>Lipoproteins - metabolism</topic><topic>Pam3Cys</topic><topic>Peptides</topic><topic>Toll-Like Receptor 2 - genetics</topic><topic>Toll-Like Receptor 2 - metabolism</topic><topic>Triazoles - chemical synthesis</topic><topic>Triazoles - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nalla, Naresh</creatorcontrib><creatorcontrib>Pallavi, Preethi</creatorcontrib><creatorcontrib>Reddy, Bonam Srinivasa</creatorcontrib><creatorcontrib>Miryala, Sreekanth</creatorcontrib><creatorcontrib>Naveen Kumar, V.</creatorcontrib><creatorcontrib>Mahboob, Mohammed</creatorcontrib><creatorcontrib>Halmuthur, M. Sampath Kumar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nalla, Naresh</au><au>Pallavi, Preethi</au><au>Reddy, Bonam Srinivasa</au><au>Miryala, Sreekanth</au><au>Naveen Kumar, V.</au><au>Mahboob, Mohammed</au><au>Halmuthur, M. Sampath Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>23</volume><issue>17</issue><spage>5846</spage><epage>5855</epage><pages>5846-5855</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate–Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26234903</pmid><doi>10.1016/j.bmc.2015.06.070</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2015-09, Vol.23 (17), p.5846-5855 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_pubmed_primary_26234903 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adjuvants Carbohydrate Click chemistry Cytokines Drug Design Lipoproteins - metabolism Pam3Cys Peptides Toll-Like Receptor 2 - genetics Toll-Like Receptor 2 - metabolism Triazoles - chemical synthesis Triazoles - chemistry |
| title | Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate–Pam3Cys conjugates as TLR2 agonists |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-30T17%3A35%3A29IST&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=Design,%20synthesis%20and%20immunological%20evaluation%20of%201,2,3-triazole-tethered%20carbohydrate%E2%80%93Pam3Cys%20conjugates%20as%20TLR2%20agonists&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Nalla,%20Naresh&rft.date=2015-09-01&rft.volume=23&rft.issue=17&rft.spage=5846&rft.epage=5855&rft.pages=5846-5855&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2015.06.070&rft_dat=%3Celsevier_pubme%3ES0968089615005647%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/26234903&rft_els_id=S0968089615005647&rfr_iscdi=true |