Characterization of the macrocyclic carbon suboxide factors as potent Na,K-ATPase and SR Ca-ATPase inhibitors.
Recently discovered macrocyclic carbon suboxide (MCS) factors with the general formula (C(3)O(2))(n) were found to strongly inhibit rabbit and rat Na,K-ATPase as well as SR Ca-ATPase. Highly active MCS factors were obtained by a base/acid treatment of their lipophilic precursor isolated from plants. In the ESI-MS spectra, the dominant molar mass ion of 431 Da corresponds to a 1:1 complex of the carbon suboxide hexamer (n=6; M(r)=408 Da) with a Na(+) ion. Additional mass ions identified in positive and negative ion mode were assigned as complexes of the MCS hexamer (n=6) and octamer (n=8) with Na(+) or with TFA(-) in various ratios. The dominant mass ion values of these active MCS factors from plants are also found in mass spectra of previously described endogenous digitalis-like factors (EDLF) from animals. This would suggest that ubiquitously distributed MCS factors may function as putative endogenous regulatory substances of Na,K-ATPase and possibly of other ATPases. With the symmetric display of several equivalent carbonyl or hydroxy groups, the structure of MCS factors is particularly suited for interactions with proteins and other bio-molecules. This could explain the high biological activity and the unusual properties of the MCS factors.
Kerek
Franz
F
AG Bioorganic Chemistry, Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Munich, Germany. franz.kerek@rzg.mpg.de
Stimac
Robert
R
Apell
Hans-Jürgen
HJ
Freudenmann
Frank
F
Moroder
Luis
L
D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D017554:Carbon Compounds, Inorganic / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D010087:Oxides / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
D017554:Carbon Compounds, Inorganic; D004791:Enzyme Inhibitors; D010087:Oxides; C118683:carbon suboxide; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase