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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
1997-10-8
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pubmed:abstractText |
Synthesis and pharmacological properties of new potent direct activators of heterotrimeric G proteins are described. Compounds were synthesized from protected amino acids with alkylamines using coupling reagents (CDI, DCC, and EDC). Alkyl-substituted amino acid amides and their corresponding di- and triamines were subjected to structure-activity analysis. All compounds activated membrane-bound HL-60 GTPases in a pertussis toxin-sensitive fashion. This suggests a specific effect of compounds on the carboxy terminus of a defined subclass of heterotrimeric G proteins, i.e., members of the G alpha i subfamily. Elongation of the alkyl chain and increasing the number of amino groups enhanced the potency of compounds on HL-60 membrane-bound GTPase. N-(2,5-Diaminopentyl)dodecylamine (21) was selected to study its mode of action employing purified pertussis toxin-sensitive G proteins. It stimulated G alpha subunits by inducing the release of bound GDP. In contrast to receptors G beta gamma complexes were not required for 21-mediated activation of G alpha. Moderate isoform selectivity of its action was observed within a group of highly homologous members of the Gi subfamily with G alpha o1 being activated at lowest concentrations, whereas higher concentrations were necessary for the stimulation of G alpha i1 or transducin. We conclude that these compounds represent important tools for studying G protein-dependent cellular functions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Amines,
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/Wasp Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/mastoparan
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3130-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9301677-Amides,
pubmed-meshheading:9301677-Amines,
pubmed-meshheading:9301677-Animals,
pubmed-meshheading:9301677-Bucladesine,
pubmed-meshheading:9301677-Cell Line,
pubmed-meshheading:9301677-Cell Membrane,
pubmed-meshheading:9301677-Enzyme Activation,
pubmed-meshheading:9301677-GTP Phosphohydrolases,
pubmed-meshheading:9301677-GTP-Binding Proteins,
pubmed-meshheading:9301677-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:9301677-Guanosine Triphosphate,
pubmed-meshheading:9301677-HL-60 Cells,
pubmed-meshheading:9301677-Humans,
pubmed-meshheading:9301677-Indicators and Reagents,
pubmed-meshheading:9301677-Macromolecular Substances,
pubmed-meshheading:9301677-Molecular Structure,
pubmed-meshheading:9301677-Peptides,
pubmed-meshheading:9301677-Pertussis Toxin,
pubmed-meshheading:9301677-Recombinant Proteins,
pubmed-meshheading:9301677-Spodoptera,
pubmed-meshheading:9301677-Structure-Activity Relationship,
pubmed-meshheading:9301677-Transfection,
pubmed-meshheading:9301677-Virulence Factors, Bordetella,
pubmed-meshheading:9301677-Wasp Venoms
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pubmed:year |
1997
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pubmed:articleTitle |
Alkyl-substituted amino acid amides and analogous di- and triamines: new non-peptide G protein activators.
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pubmed:affiliation |
Institut für Pharmazie I, Freie Universität Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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