J. Biochem, 1997, Vol. 121, No. 4 779-786
© 1997 Japanese Biochemical Society
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Structural Feature of the Major but Not Cytokine-Inducing Molecular Species of Lipoteichoic Acid1
*Department of Chemistry, Graduate School of Science, Osaka University Toyonaka, Osaka 560
Department of Microbiology and Immunology, Tohoku University Dental School Aoba-ku, Sendai 980-77
Tokyo Institute for Immunopharmacology Inc. Toshima-ku, Tokyo 171
§Osaka College of Medical Technology Kita-ku, Osaka 530
2To whom correspondence should be addressed. Tel: +81-6-850-5388, Fax: +81-6 850-5419 E-Mail: skus{at}chem.sci.osaka-u.ac.jp
Previously, lipoteichoic acid (LTA) of Enterococcus hirae was found to exhibit definite cytokine-inducing activity but synthetic specimens which share the fundamental structural principles proposed for LTA had no corresponding activity. We also showed recently that several minor components totally less than 5% of the LTA fraction from E. hirae ATCC 9790 possessed the activity, whereas the major component (over 90%) did not [Suda, Y., Tochio, H., Kawano, K., Takada, H., Yoshida, T., Kotani, S., and Kusumoto, S. (1995) FEMS Immun. Med. Microbiol. 12, 97–112]. In the present study, the structure of the major component of LTA was studied in an attempt to elucidate the reason for the lack of the activity in the synthetic compounds. The major component of the LTA was first digested by hydrofluoric acid hydrolysis to cleave phosphodiester linkages present. The hydrolysis products were separated and characterized by means of NMR and MS. The linkage positions of the original phosphodiesters were determined from the NMR spectra of an alkali-treated product without hydrofluoric acid degradation. The compound was proved to consist of 1,3-linked poly(glycerophosphate) and a lipid anchor, Glc(
l-2)Glc(l-3)acyl2Gro, the former being linked to the 6-position of the distal glucose of the latter. The 2-position of the glycerol residues in the glycerophosphate part were substituted by oligoglucose esterified partially with alanine. The gross structure elucidated here thus coincides with the previous conclusion described by Fischer [Fischer, W. (1990) in Glycolipids, Phosphoglycolipids and Sulfoglycolipids (Kates, M., ed.) pp. 123–234, Plenum Press, New York]. Thus, the molecular species with this so-called "LTA structure" is not responsible for the cytokine-inducing activity.
1This research was supported in parts by Grants-in-Aid for Scientific Research (No. 05403035 to S.K.) and for Scientific Research on Priority Areas (No. 05274102 to Y.S.) from the Ministry of Education, Science, Sports and Culture of Japan and by a grant from Chugai Pharmaceutical Co. Ltd., Tokyo
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