60209-20-3Relevant academic research and scientific papers
Alkyl-substituted amino acid amides and analogous di- and triamines: New non-peptide G protein activators
Leschke, Christian,Storm, Rüdiger,Breitweg-Lehmann, Evelyn,Exner, Torsten,Nürnberg, Bernd,Schunack, Walter
, p. 3130 - 3139 (1997)
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 Gα(i) subfamily. Elongation of the alkyl chain and increasing the number of amino groups enhanced the potency of compounds on HL-60 membranes-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 Cα subunits by inducing the release of bound GDP. In contrast to receptors Gβγ complexes were not required for 21-mediated activation of Gα. Moderate isoform selectivity of its action was observed within a group of highly homologous members of the G(i) subfamily with Gα(o1) being activated at lowest concentrations, whereas higher concentrations were necessary for the stimulation of Gα(i1) or transducin. We conclude that these compounds represent important tools for studying G protein-dependent cellular functions.
