Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships
Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl ri...
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| Veröffentlicht in: | Journal of medicinal chemistry 1984-06, Vol.27 (6), p.754-757 |
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| container_title | Journal of medicinal chemistry |
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| creator | Shreeve, S. Martin Veitch, G. B. A Hemsworth, Brian A |
| description | Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro. |
| doi_str_mv | 10.1021/jm00372a009 |
| format | Article |
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Martin ; Veitch, G. B. A ; Hemsworth, Brian A</creator><creatorcontrib>Shreeve, S. Martin ; Veitch, G. B. A ; Hemsworth, Brian A</creatorcontrib><description>Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00372a009</identifier><identifier>PMID: 6737417</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Acetylation ; Analytical, structural and metabolic biochemistry ; Animals ; Biological and medical sciences ; Choline - pharmacology ; Choline O-Acetyltransferase - metabolism ; Enzymes and enzyme inhibitors ; Fundamental and applied biological sciences. Psychology ; Hemicholinium 3 - analogs & derivatives ; Hemicholinium 3 - pharmacology ; Kinetics ; Rats ; Structure-Activity Relationship ; Transferases</subject><ispartof>Journal of medicinal chemistry, 1984-06, Vol.27 (6), p.754-757</ispartof><rights>1985 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-faf58ad9584901dd46b6f3bcbba55ace6013229a58be38c59e400268f718f38d3</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/jm00372a009$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00372a009$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8994946$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6737417$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shreeve, S. Martin</creatorcontrib><creatorcontrib>Veitch, G. B. A</creatorcontrib><creatorcontrib>Hemsworth, Brian A</creatorcontrib><title>Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro.</description><subject>Acetylation</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Choline - pharmacology</subject><subject>Choline O-Acetyltransferase - metabolism</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemicholinium 3 - analogs & derivatives</subject><subject>Hemicholinium 3 - pharmacology</subject><subject>Kinetics</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>Transferases</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1984</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0M1rFDEYBvAgSl1bT56FHKQeZDQf85Hx1i5axYIFK4iXkMm8YbPOTNa8mdL9742dZfHgKYfnx5PkIeQFZ285E_zddmRMNsIw1j4iK14JVpSKlY_JijEhClEL-ZQ8Q9yy7LiQJ-SkbmRT8mZF7i8spP1gkg8TDY5iGIFO4Q4GuoHR200Y_OTnkdow7sI89Ui7fVbD3A1AlxioeShJ0UzoIBqE9xRTnG2aIxTGJn_n055GWO7Bjd_hGXnizIDw_HCeku8fP9yuPxXXX68-ry-uCyOVTIUzrlKmbytVtoz3fVl3tZOd7TpTVfnamnEpRGsq1YFUtmqhzJ-ulWu4clL18pScL727GH7PgEmPHi0Mg5kgzKgV55I1ssrwzQJtDIgRnN5FP5q415zpvzvrf3bO-uWhdu5G6I_2MGzOXx1yg9YMLk9jPR6ZatuyLevMioV5THB_jE389dBU6dubb5rJ9dWXyx9K_8z-9eKNRb0Nc5zydv994B8cV6QP</recordid><startdate>198406</startdate><enddate>198406</enddate><creator>Shreeve, S. Martin</creator><creator>Veitch, G. B. A</creator><creator>Hemsworth, Brian A</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>198406</creationdate><title>Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships</title><author>Shreeve, S. Martin ; Veitch, G. B. A ; Hemsworth, Brian A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a383t-faf58ad9584901dd46b6f3bcbba55ace6013229a58be38c59e400268f718f38d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>Acetylation</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Choline - pharmacology</topic><topic>Choline O-Acetyltransferase - metabolism</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hemicholinium 3 - analogs & derivatives</topic><topic>Hemicholinium 3 - pharmacology</topic><topic>Kinetics</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><topic>Transferases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shreeve, S. Martin</creatorcontrib><creatorcontrib>Veitch, G. B. A</creatorcontrib><creatorcontrib>Hemsworth, Brian A</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>Shreeve, S. Martin</au><au>Veitch, G. B. A</au><au>Hemsworth, Brian A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1984-06</date><risdate>1984</risdate><volume>27</volume><issue>6</issue><spage>754</spage><epage>757</epage><pages>754-757</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>6737417</pmid><doi>10.1021/jm00372a009</doi><tpages>4</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1984-06, Vol.27 (6), p.754-757 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Acetylation Analytical, structural and metabolic biochemistry Animals Biological and medical sciences Choline - pharmacology Choline O-Acetyltransferase - metabolism Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Hemicholinium 3 - analogs & derivatives Hemicholinium 3 - pharmacology Kinetics Rats Structure-Activity Relationship Transferases |
| title | Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships |
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