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Characterization of the macrocyclic carbon suboxide factors as potent Na,K-ATPase and SR Ca-ATPase inhibitors

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons78206

Kerek,  F.
Moroder, Luis / Bioorganic Chemistry, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons77973

Freudenmann,  F.
Moroder, Luis / Bioorganic Chemistry, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78419

Moroder,  L.
Moroder, Luis / Bioorganic Chemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Kerek, F., Stimac, R., Apell, H. J., Freudenmann, F., & Moroder, L. (2002). Characterization of the macrocyclic carbon suboxide factors as potent Na,K-ATPase and SR Ca-ATPase inhibitors. Biochimica et Biophysica Acta-Biomembranes, 1567(1-2), 213-220.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-6D9B-B
Zusammenfassung
Recently discovered macrocyclic carbon suboxide (MCS) factors with the general formula (C3O2)(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. (C) 2002 Elsevier Science B.V. All rights reserved.