Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom
The total synthesis of the Gla-containing "sleeper" peptide (Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2 ) from Conus geographus is described. A new strategy for the synthesis of acid-sensitive peptide amides was developed, which allowed complete deprotection an...
Gespeichert in:
| Veröffentlicht in: | Biochemistry (Easton) 1987-12, Vol.26 (26), p.8508-8512 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 8512 |
|---|---|
| container_issue | 26 |
| container_start_page | 8508 |
| container_title | Biochemistry (Easton) |
| container_volume | 26 |
| creator | Rivier, Jean Galyean, Robert Simon, Lajos Cruz, Lourdes J Olivera, Baldomero M Gray, William R |
| description | The total synthesis of the Gla-containing "sleeper" peptide (Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2 ) from Conus geographus is described. A new strategy for the synthesis of acid-sensitive peptide amides was developed, which allowed complete deprotection and cleavage of the L-gamma-carboxyglutamate-containing peptide from the 2,4-dimethoxybenzhydrylamine resin. Synthetic sleeper peptide, after preparative high-performance liquid chromatography (HPLC) purification, was shown to be identical with the native peptide by all criteria (coelution experiments of HPLC, sequence analysis, and biological activity). In addition, a developmental switch in the behavioral symptoms induced by the peptide after intracerebral administration in mice was documented. At low doses of the peptide (4-30 pmol/g), a sleeplike state was induced in mice under 2 weeks old; in contrast, older mice became markedly hyperactive. It is proposed that, in the presence of Ca2+, the sleeper peptide assumes an alpha-helical configuration in which all the gamma-carboxyglutamate residues are located on the same side of the alpha-helix. |
| doi_str_mv | 10.1021/bi00400a002 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_14920695</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>14920695</sourcerecordid><originalsourceid>FETCH-LOGICAL-a414t-4e1af53fbcc21746b65b9df6fccff3ef186fb49a7f7f3c23c3575f2432a247e53</originalsourceid><addsrcrecordid>eNpt0M-LEzEUB_AgylpXT56FsIgeZGp-TbJzlKKrS1HB8RzepEmbdSYZk4xsvft_O6WlePCUF74fHo8vQs8pWVLC6NvOEyIIAULYA7SgNSOVaJr6IVoQQmTFGkkeoyc535GDU-ICXXAhmFRsgf60sUCP8z6Unc0-Ywgb7KY0_xI2O0hgik3-NxQfA44OzwFebmEYYFkZSF2832_7qcAAxVYmhgI--LDFV7m3drTpCo92LH5jsUtxwKsYpoy3Nm4TjLt5_GVDHJ6iRw76bJ-d3kv0_cP7dvWxWn-5-bR6t65AUFEqYSm4mrvOGEaVkJ2su2bjpDPGOW4dvZauEw0opxw3jBteq9oxwRkwoWzNL9Gr494xxZ-TzUUPPhvb9xBsnLKmomFENgf45ghNijkn6_SY_ABprynRh9L1P6XP-sVp7dQNdnO2p5bn_OUph2ygdwmC8fnM1DVjUoqZVUfmc7H35xjSDy0VV7Vuv37Tt_ymvf285rqd_eujB5P1XZxSmLv774F_AUwHp-g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>14920695</pqid></control><display><type>article</type><title>Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom</title><source>ACS Publications</source><source>MEDLINE</source><creator>Rivier, Jean ; Galyean, Robert ; Simon, Lajos ; Cruz, Lourdes J ; Olivera, Baldomero M ; Gray, William R</creator><creatorcontrib>Rivier, Jean ; Galyean, Robert ; Simon, Lajos ; Cruz, Lourdes J ; Olivera, Baldomero M ; Gray, William R</creatorcontrib><description>The total synthesis of the Gla-containing "sleeper" peptide (Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2 ) from Conus geographus is described. A new strategy for the synthesis of acid-sensitive peptide amides was developed, which allowed complete deprotection and cleavage of the L-gamma-carboxyglutamate-containing peptide from the 2,4-dimethoxybenzhydrylamine resin. Synthetic sleeper peptide, after preparative high-performance liquid chromatography (HPLC) purification, was shown to be identical with the native peptide by all criteria (coelution experiments of HPLC, sequence analysis, and biological activity). In addition, a developmental switch in the behavioral symptoms induced by the peptide after intracerebral administration in mice was documented. At low doses of the peptide (4-30 pmol/g), a sleeplike state was induced in mice under 2 weeks old; in contrast, older mice became markedly hyperactive. It is proposed that, in the presence of Ca2+, the sleeper peptide assumes an alpha-helical configuration in which all the gamma-carboxyglutamate residues are located on the same side of the alpha-helix.</description><identifier>ISSN: 0006-2960</identifier><identifier>EISSN: 1520-4995</identifier><identifier>DOI: 10.1021/bi00400a002</identifier><identifier>PMID: 3442672</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>1-Carboxyglutamic Acid ; Amino Acid Sequence ; Aminoacids, peptides. Hormones. Neuropeptides ; Analytical, structural and metabolic biochemistry ; Animals ; Biological and medical sciences ; biological poisons ; calcium ; Chromatography, High Pressure Liquid ; Conotoxins ; Conus geographus ; Fundamental and applied biological sciences. Psychology ; Indicators and Reagents ; Marine ; Mice ; Mollusk Venoms - chemical synthesis ; Mollusk Venoms - pharmacology ; peptides ; Protein Conformation ; Proteins ; Sleep - drug effects ; sleeper peptide</subject><ispartof>Biochemistry (Easton), 1987-12, Vol.26 (26), p.8508-8512</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a414t-4e1af53fbcc21746b65b9df6fccff3ef186fb49a7f7f3c23c3575f2432a247e53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bi00400a002$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bi00400a002$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2751,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7822664$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3442672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rivier, Jean</creatorcontrib><creatorcontrib>Galyean, Robert</creatorcontrib><creatorcontrib>Simon, Lajos</creatorcontrib><creatorcontrib>Cruz, Lourdes J</creatorcontrib><creatorcontrib>Olivera, Baldomero M</creatorcontrib><creatorcontrib>Gray, William R</creatorcontrib><title>Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom</title><title>Biochemistry (Easton)</title><addtitle>Biochemistry</addtitle><description>The total synthesis of the Gla-containing "sleeper" peptide (Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2 ) from Conus geographus is described. A new strategy for the synthesis of acid-sensitive peptide amides was developed, which allowed complete deprotection and cleavage of the L-gamma-carboxyglutamate-containing peptide from the 2,4-dimethoxybenzhydrylamine resin. Synthetic sleeper peptide, after preparative high-performance liquid chromatography (HPLC) purification, was shown to be identical with the native peptide by all criteria (coelution experiments of HPLC, sequence analysis, and biological activity). In addition, a developmental switch in the behavioral symptoms induced by the peptide after intracerebral administration in mice was documented. At low doses of the peptide (4-30 pmol/g), a sleeplike state was induced in mice under 2 weeks old; in contrast, older mice became markedly hyperactive. It is proposed that, in the presence of Ca2+, the sleeper peptide assumes an alpha-helical configuration in which all the gamma-carboxyglutamate residues are located on the same side of the alpha-helix.</description><subject>1-Carboxyglutamic Acid</subject><subject>Amino Acid Sequence</subject><subject>Aminoacids, peptides. Hormones. Neuropeptides</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>biological poisons</subject><subject>calcium</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Conotoxins</subject><subject>Conus geographus</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Indicators and Reagents</subject><subject>Marine</subject><subject>Mice</subject><subject>Mollusk Venoms - chemical synthesis</subject><subject>Mollusk Venoms - pharmacology</subject><subject>peptides</subject><subject>Protein Conformation</subject><subject>Proteins</subject><subject>Sleep - drug effects</subject><subject>sleeper peptide</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1987</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0M-LEzEUB_AgylpXT56FsIgeZGp-TbJzlKKrS1HB8RzepEmbdSYZk4xsvft_O6WlePCUF74fHo8vQs8pWVLC6NvOEyIIAULYA7SgNSOVaJr6IVoQQmTFGkkeoyc535GDU-ICXXAhmFRsgf60sUCP8z6Unc0-Ywgb7KY0_xI2O0hgik3-NxQfA44OzwFebmEYYFkZSF2832_7qcAAxVYmhgI--LDFV7m3drTpCo92LH5jsUtxwKsYpoy3Nm4TjLt5_GVDHJ6iRw76bJ-d3kv0_cP7dvWxWn-5-bR6t65AUFEqYSm4mrvOGEaVkJ2su2bjpDPGOW4dvZauEw0opxw3jBteq9oxwRkwoWzNL9Gr494xxZ-TzUUPPhvb9xBsnLKmomFENgf45ghNijkn6_SY_ABprynRh9L1P6XP-sVp7dQNdnO2p5bn_OUph2ygdwmC8fnM1DVjUoqZVUfmc7H35xjSDy0VV7Vuv37Tt_ymvf285rqd_eujB5P1XZxSmLv774F_AUwHp-g</recordid><startdate>19871201</startdate><enddate>19871201</enddate><creator>Rivier, Jean</creator><creator>Galyean, Robert</creator><creator>Simon, Lajos</creator><creator>Cruz, Lourdes J</creator><creator>Olivera, Baldomero M</creator><creator>Gray, William R</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QL</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>19871201</creationdate><title>Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom</title><author>Rivier, Jean ; Galyean, Robert ; Simon, Lajos ; Cruz, Lourdes J ; Olivera, Baldomero M ; Gray, William R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-4e1af53fbcc21746b65b9df6fccff3ef186fb49a7f7f3c23c3575f2432a247e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1987</creationdate><topic>1-Carboxyglutamic Acid</topic><topic>Amino Acid Sequence</topic><topic>Aminoacids, peptides. Hormones. Neuropeptides</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>biological poisons</topic><topic>calcium</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Conotoxins</topic><topic>Conus geographus</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Indicators and Reagents</topic><topic>Marine</topic><topic>Mice</topic><topic>Mollusk Venoms - chemical synthesis</topic><topic>Mollusk Venoms - pharmacology</topic><topic>peptides</topic><topic>Protein Conformation</topic><topic>Proteins</topic><topic>Sleep - drug effects</topic><topic>sleeper peptide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rivier, Jean</creatorcontrib><creatorcontrib>Galyean, Robert</creatorcontrib><creatorcontrib>Simon, Lajos</creatorcontrib><creatorcontrib>Cruz, Lourdes J</creatorcontrib><creatorcontrib>Olivera, Baldomero M</creatorcontrib><creatorcontrib>Gray, William R</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rivier, Jean</au><au>Galyean, Robert</au><au>Simon, Lajos</au><au>Cruz, Lourdes J</au><au>Olivera, Baldomero M</au><au>Gray, William R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>1987-12-01</date><risdate>1987</risdate><volume>26</volume><issue>26</issue><spage>8508</spage><epage>8512</epage><pages>8508-8512</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>The total synthesis of the Gla-containing "sleeper" peptide (Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2 ) from Conus geographus is described. A new strategy for the synthesis of acid-sensitive peptide amides was developed, which allowed complete deprotection and cleavage of the L-gamma-carboxyglutamate-containing peptide from the 2,4-dimethoxybenzhydrylamine resin. Synthetic sleeper peptide, after preparative high-performance liquid chromatography (HPLC) purification, was shown to be identical with the native peptide by all criteria (coelution experiments of HPLC, sequence analysis, and biological activity). In addition, a developmental switch in the behavioral symptoms induced by the peptide after intracerebral administration in mice was documented. At low doses of the peptide (4-30 pmol/g), a sleeplike state was induced in mice under 2 weeks old; in contrast, older mice became markedly hyperactive. It is proposed that, in the presence of Ca2+, the sleeper peptide assumes an alpha-helical configuration in which all the gamma-carboxyglutamate residues are located on the same side of the alpha-helix.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3442672</pmid><doi>10.1021/bi00400a002</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-2960 |
| ispartof | Biochemistry (Easton), 1987-12, Vol.26 (26), p.8508-8512 |
| issn | 0006-2960 1520-4995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_14920695 |
| source | ACS Publications; MEDLINE |
| subjects | 1-Carboxyglutamic Acid Amino Acid Sequence Aminoacids, peptides. Hormones. Neuropeptides Analytical, structural and metabolic biochemistry Animals Biological and medical sciences biological poisons calcium Chromatography, High Pressure Liquid Conotoxins Conus geographus Fundamental and applied biological sciences. Psychology Indicators and Reagents Marine Mice Mollusk Venoms - chemical synthesis Mollusk Venoms - pharmacology peptides Protein Conformation Proteins Sleep - drug effects sleeper peptide |
| title | Total synthesis and further characterization of the .gamma.-carboxyglutamate-containing "sleeper" peptide from Conus geographus venom |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T03%3A01%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Total%20synthesis%20and%20further%20characterization%20of%20the%20.gamma.-carboxyglutamate-containing%20%22sleeper%22%20peptide%20from%20Conus%20geographus%20venom&rft.jtitle=Biochemistry%20(Easton)&rft.au=Rivier,%20Jean&rft.date=1987-12-01&rft.volume=26&rft.issue=26&rft.spage=8508&rft.epage=8512&rft.pages=8508-8512&rft.issn=0006-2960&rft.eissn=1520-4995&rft_id=info:doi/10.1021/bi00400a002&rft_dat=%3Cproquest_cross%3E14920695%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=14920695&rft_id=info:pmid/3442672&rfr_iscdi=true |