Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase
The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of revers...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2005-07, Vol.48 (14), p.4670-4678 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4678 |
|---|---|
| container_issue | 14 |
| container_start_page | 4670 |
| container_title | Journal of medicinal chemistry |
| container_volume | 48 |
| creator | Rossiter, Sharon Smith, Caroline L Malaki, Mohammed Nandi, Manasi Gill, Herpreet Leiper, James M Vallance, Patrick Selwood, David L |
| description | The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated. |
| doi_str_mv | 10.1021/jm050187a |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68009001</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68009001</sourcerecordid><originalsourceid>FETCH-LOGICAL-a381t-7088c16f54347be0d6c53af4182db2df15e031a6c70620e00253c30003bb93d83</originalsourceid><addsrcrecordid>eNptkMtOwzAQRS0EgvJY8AMoG5BYBMZ2nKRLoLwkEEgtC1bWxJlQlzzAThD9e1K1oiyYjaXx0dWdw9ghhzMOgp_PKlDA0wQ32IArAWGUQrTJBgBChCIWcoftej8DAMmF3GY7PIbFyAF7HVNJprVfFIy7zLcOWwov0VMe3NdTm9m2cT5oiuARqwpLi3UwshW103mJ7s3Wtqb1orJ1M53nrin7gH22VWDp6WD17rGXm-vJ1V348HR7f3XxEKJMeRsmkKaGx4WKZJRkBHlslMQi4qnIM5EXXFHfGmOTQCyA-pOUNHJRPsuGMk_lHjtZ5n645rMj3-rKekNliTU1nddxCjAE4D14ugSNa7x3VOgPZyt0c81BLzzqX489e7QK7bKK8jW5EtcDxysAvcGycFgb6_9wQyU5T3ouXHLWt_T9-4_uXceJTJSePI_1ZCy4mtyM9Gidi8brWdO5unf3T8Ef-QCVXQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68009001</pqid></control><display><type>article</type><title>Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase</title><source>ACS Publications</source><source>MEDLINE</source><creator>Rossiter, Sharon ; Smith, Caroline L ; Malaki, Mohammed ; Nandi, Manasi ; Gill, Herpreet ; Leiper, James M ; Vallance, Patrick ; Selwood, David L</creator><creatorcontrib>Rossiter, Sharon ; Smith, Caroline L ; Malaki, Mohammed ; Nandi, Manasi ; Gill, Herpreet ; Leiper, James M ; Vallance, Patrick ; Selwood, David L</creatorcontrib><description>The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm050187a</identifier><identifier>PMID: 16000003</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Amidohydrolases - antagonists & inhibitors ; Animals ; Arginine - analogs & derivatives ; Arginine - blood ; Arginine - chemical synthesis ; Arginine - pharmacology ; Biological and medical sciences ; Cell Line ; Cell Survival - drug effects ; In Vitro Techniques ; Kidney - drug effects ; Kidney - enzymology ; Male ; Medical sciences ; Miscellaneous ; Nitric Oxide Synthase - antagonists & inhibitors ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred WKY ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 2005-07, Vol.48 (14), p.4670-4678</ispartof><rights>Copyright © 2005 American Chemical Society</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a381t-7088c16f54347be0d6c53af4182db2df15e031a6c70620e00253c30003bb93d83</citedby><cites>FETCH-LOGICAL-a381t-7088c16f54347be0d6c53af4182db2df15e031a6c70620e00253c30003bb93d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm050187a$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm050187a$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16953117$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16000003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rossiter, Sharon</creatorcontrib><creatorcontrib>Smith, Caroline L</creatorcontrib><creatorcontrib>Malaki, Mohammed</creatorcontrib><creatorcontrib>Nandi, Manasi</creatorcontrib><creatorcontrib>Gill, Herpreet</creatorcontrib><creatorcontrib>Leiper, James M</creatorcontrib><creatorcontrib>Vallance, Patrick</creatorcontrib><creatorcontrib>Selwood, David L</creatorcontrib><title>Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.</description><subject>Amidohydrolases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - blood</subject><subject>Arginine - chemical synthesis</subject><subject>Arginine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>In Vitro Techniques</subject><subject>Kidney - drug effects</subject><subject>Kidney - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Inbred WKY</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkMtOwzAQRS0EgvJY8AMoG5BYBMZ2nKRLoLwkEEgtC1bWxJlQlzzAThD9e1K1oiyYjaXx0dWdw9ghhzMOgp_PKlDA0wQ32IArAWGUQrTJBgBChCIWcoftej8DAMmF3GY7PIbFyAF7HVNJprVfFIy7zLcOWwov0VMe3NdTm9m2cT5oiuARqwpLi3UwshW103mJ7s3Wtqb1orJ1M53nrin7gH22VWDp6WD17rGXm-vJ1V348HR7f3XxEKJMeRsmkKaGx4WKZJRkBHlslMQi4qnIM5EXXFHfGmOTQCyA-pOUNHJRPsuGMk_lHjtZ5n645rMj3-rKekNliTU1nddxCjAE4D14ugSNa7x3VOgPZyt0c81BLzzqX489e7QK7bKK8jW5EtcDxysAvcGycFgb6_9wQyU5T3ouXHLWt_T9-4_uXceJTJSePI_1ZCy4mtyM9Gidi8brWdO5unf3T8Ef-QCVXQ</recordid><startdate>20050714</startdate><enddate>20050714</enddate><creator>Rossiter, Sharon</creator><creator>Smith, Caroline L</creator><creator>Malaki, Mohammed</creator><creator>Nandi, Manasi</creator><creator>Gill, Herpreet</creator><creator>Leiper, James M</creator><creator>Vallance, Patrick</creator><creator>Selwood, David L</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>7X8</scope></search><sort><creationdate>20050714</creationdate><title>Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase</title><author>Rossiter, Sharon ; Smith, Caroline L ; Malaki, Mohammed ; Nandi, Manasi ; Gill, Herpreet ; Leiper, James M ; Vallance, Patrick ; Selwood, David L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a381t-7088c16f54347be0d6c53af4182db2df15e031a6c70620e00253c30003bb93d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amidohydrolases - antagonists & inhibitors</topic><topic>Animals</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - blood</topic><topic>Arginine - chemical synthesis</topic><topic>Arginine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>In Vitro Techniques</topic><topic>Kidney - drug effects</topic><topic>Kidney - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred WKY</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rossiter, Sharon</creatorcontrib><creatorcontrib>Smith, Caroline L</creatorcontrib><creatorcontrib>Malaki, Mohammed</creatorcontrib><creatorcontrib>Nandi, Manasi</creatorcontrib><creatorcontrib>Gill, Herpreet</creatorcontrib><creatorcontrib>Leiper, James M</creatorcontrib><creatorcontrib>Vallance, Patrick</creatorcontrib><creatorcontrib>Selwood, David L</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>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rossiter, Sharon</au><au>Smith, Caroline L</au><au>Malaki, Mohammed</au><au>Nandi, Manasi</au><au>Gill, Herpreet</au><au>Leiper, James M</au><au>Vallance, Patrick</au><au>Selwood, David L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2005-07-14</date><risdate>2005</risdate><volume>48</volume><issue>14</issue><spage>4670</spage><epage>4678</epage><pages>4670-4678</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>16000003</pmid><doi>10.1021/jm050187a</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2005-07, Vol.48 (14), p.4670-4678 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68009001 |
| source | ACS Publications; MEDLINE |
| subjects | Amidohydrolases - antagonists & inhibitors Animals Arginine - analogs & derivatives Arginine - blood Arginine - chemical synthesis Arginine - pharmacology Biological and medical sciences Cell Line Cell Survival - drug effects In Vitro Techniques Kidney - drug effects Kidney - enzymology Male Medical sciences Miscellaneous Nitric Oxide Synthase - antagonists & inhibitors Pharmacology. Drug treatments Rats Rats, Inbred WKY Structure-Activity Relationship |
| title | Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T05%3A12%3A30IST&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=Selective%20Substrate-Based%20Inhibitors%20of%20Mammalian%20Dimethylarginine%20Dimethylaminohydrolase&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Rossiter,%20Sharon&rft.date=2005-07-14&rft.volume=48&rft.issue=14&rft.spage=4670&rft.epage=4678&rft.pages=4670-4678&rft.issn=0022-2623&rft.eissn=1520-4804&rft.coden=JMCMAR&rft_id=info:doi/10.1021/jm050187a&rft_dat=%3Cproquest_cross%3E68009001%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=68009001&rft_id=info:pmid/16000003&rfr_iscdi=true |