Oligosaccharide-specific receptors for gangliosides in the central nervous system
Synthetic ganglioside-derivatized proteins were prepared, radiolabeled, and used as ligands to search for specific receptors on rat brain membranes. Chemical derivatization schemes were designed to covalently link gangliosides (specifically, G{sub T1b}) to bovine serum albumin (BSA) via their ceramide portions leaving the glycolipid oligosaccharides intact and limiting the ability of the ganglioside moiety to interact with brain membranes non-specifically by insertion or hydrophobic adsorption. Following characterization and tyrosine-radioiodination, {sup 125}I-(G{sub T1b}){sub 4} BSA (BSA derivatized with 4 G{sub T1b} moieties/protein molecule), revealed a high affinity and saturable binding site on rat brain membranes. Pretreatment of brain membranes with low concentrations of trypsin blocked binding, consistent with the presence of a proteinaceous ganglioside-receptor. The most potent lipid inhibitors of {sup 125}I-(G{sub T1b}){sub 4}BSA binding were the gangliosides G{sub T1b}, G{sub D1b}, and G{sub Q1b} which share common structural features in their oligosaccharide portions; maximal inhibitory potency required a full length gangliotetraose oligosaccharide core and {alpha}2-8 linked sialic acid.
- Research Organization:
- Johns Hopkins Univ., Baltimore, MD (USA)
- OSTI ID:
- 6795060
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GANGLIOSIDES
RECEPTORS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BRAIN
CELL MEMBRANES
IODINE 125
LIGANDS
OLIGOSACCHARIDES
RATS
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
FUNCTIONS
GLYCOLIPIDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques