Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin
- National Inst. of Health, Bethesda, MD (United States)
The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the ability to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.
- OSTI ID:
- 5015272
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:10; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMP
ANIMALS
ANTIGENS
BACTERIAL DISEASES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CARBOHYDRATES
CHOLERA
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GANGLIOSIDES
GLIOMAS
GLYCOLIPIDS
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NEOPLASMS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
OLIGOSACCHARIDES
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SEPARATION PROCESSES
SYNTHESIS
THIN-LAYER CHROMATOGRAPHY
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES