Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin
For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide...
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| Veröffentlicht in: | Journal of medicinal chemistry 1975-10, Vol.18 (10), p.1020-1022 |
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| creator | Ferger, Martha F Chan, W. Y |
| description | For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney. |
| doi_str_mv | 10.1021/jm00244a013 |
| format | Article |
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Y</creator><creatorcontrib>Ferger, Martha F ; Chan, W. Y</creatorcontrib><description>For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00244a013</identifier><identifier>PMID: 1159679</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Blood Pressure - drug effects ; Chickens ; Depression, Chemical ; Diuresis - drug effects ; Female ; In Vitro Techniques ; Leucine - chemical synthesis ; Leucine - pharmacology ; Male ; Oxytocin - analogs & derivatives ; Oxytocin - chemical synthesis ; Oxytocin - pharmacology ; Penicillamine - analogs & derivatives ; Penicillamine - chemical synthesis ; Penicillamine - pharmacology ; Rats ; Uterine Contraction - drug effects</subject><ispartof>Journal of medicinal chemistry, 1975-10, Vol.18 (10), p.1020-1022</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a354t-54db33d3f36135925337e68c282c5e2ac7dc70844f24132f5cf41a860c112ef63</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/jm00244a013$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00244a013$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1159679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferger, Martha F</creatorcontrib><creatorcontrib>Chan, W. Y</creatorcontrib><title>Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney.</description><subject>Animals</subject><subject>Blood Pressure - drug effects</subject><subject>Chickens</subject><subject>Depression, Chemical</subject><subject>Diuresis - drug effects</subject><subject>Female</subject><subject>In Vitro Techniques</subject><subject>Leucine - chemical synthesis</subject><subject>Leucine - pharmacology</subject><subject>Male</subject><subject>Oxytocin - analogs & derivatives</subject><subject>Oxytocin - chemical synthesis</subject><subject>Oxytocin - pharmacology</subject><subject>Penicillamine - analogs & derivatives</subject><subject>Penicillamine - chemical synthesis</subject><subject>Penicillamine - pharmacology</subject><subject>Rats</subject><subject>Uterine Contraction - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1975</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtPwzAQhC0EKqVw4oyUExwg4GceR2gpIIpAajkhZLmOQ12SONiJ1P57XKUCDpx2tfNpZjUAHCN4iSBGV8sSQkypgIjsgD5iGIY0gXQX9P0dhzjCZB8cOLeEEBKESQ_0EGJpFKd9MJ2uq2ahnHaBqLKgXghbCmkK86GlKILamlrZRisXmDx4Q-EkrFWlpS4KUepKXVB_KVQr_f5uVuvG-O0Q7OWicOpoOwfgdXw7G96Hk-e7h-H1JBSE0SZkNJsTkpGcRIiwFDNCYhUlEidYMoWFjDMZw4TSHFNEcM5kTpFIIigRwiqPyACcdr7-y69WuYaX2knlX6uUaR1PcMrSlGAPnnegtMY5q3JeW10Ku-YI8k2F_E-Fnj7Z2rbzUmW_bNeZ18NO165Rqx9Z2E8exSRmfPYy5eNkdPM0eoz5Jv2s44V0fGlaW_lS_k3-BqefhoU</recordid><startdate>19751001</startdate><enddate>19751001</enddate><creator>Ferger, Martha F</creator><creator>Chan, W. Y</creator><general>American Chemical Society</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>19751001</creationdate><title>Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin</title><author>Ferger, Martha F ; Chan, W. Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a354t-54db33d3f36135925337e68c282c5e2ac7dc70844f24132f5cf41a860c112ef63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1975</creationdate><topic>Animals</topic><topic>Blood Pressure - drug effects</topic><topic>Chickens</topic><topic>Depression, Chemical</topic><topic>Diuresis - drug effects</topic><topic>Female</topic><topic>In Vitro Techniques</topic><topic>Leucine - chemical synthesis</topic><topic>Leucine - pharmacology</topic><topic>Male</topic><topic>Oxytocin - analogs & derivatives</topic><topic>Oxytocin - chemical synthesis</topic><topic>Oxytocin - pharmacology</topic><topic>Penicillamine - analogs & derivatives</topic><topic>Penicillamine - chemical synthesis</topic><topic>Penicillamine - pharmacology</topic><topic>Rats</topic><topic>Uterine Contraction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferger, Martha F</creatorcontrib><creatorcontrib>Chan, W. Y</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferger, Martha F</au><au>Chan, W. Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1975-10-01</date><risdate>1975</risdate><volume>18</volume><issue>10</issue><spage>1020</spage><epage>1022</epage><pages>1020-1022</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>1159679</pmid><doi>10.1021/jm00244a013</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1975-10, Vol.18 (10), p.1020-1022 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Blood Pressure - drug effects Chickens Depression, Chemical Diuresis - drug effects Female In Vitro Techniques Leucine - chemical synthesis Leucine - pharmacology Male Oxytocin - analogs & derivatives Oxytocin - chemical synthesis Oxytocin - pharmacology Penicillamine - analogs & derivatives Penicillamine - chemical synthesis Penicillamine - pharmacology Rats Uterine Contraction - drug effects |
| title | Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin |
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