Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

Journal Article · Tue Mar 12 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00224a001· OSTI ID:5015272

Pacuszka, T; Bradley, R M; Fishman, P H ^[1]

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1. 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), Vol. 30:10; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLYCOLIPIDS
BIOSYNTHESIS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
TOXINS
RADIORECEPTOR ASSAY
AMP
CHOLERA
GANGLIOSIDES
GLIOMAS
IODINE 125
MOLECULAR STRUCTURE
OLIGOSACCHARIDES
RATS
THIN-LAYER CHROMATOGRAPHY
ANIMALS
ANTIGENS
BACTERIAL DISEASES
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SACCHARIDES
SEPARATION PROCESSES
SYNTHESIS
TOXIC MATERIALS
TRACER TECHNIQUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques