Assignment of the carbon-13 nuclear magnetic resonance spectrum of aqueous ganglioside GM1 micelles

Abstract

This article describes the natural-abundance Fourier-transform carbon-13 nuclear magnetic resonance spectrum, at 67.88 MHz, of aqueous micelles of bovine brain ganglioside GM1 of purity greater than 99%. Assignments are given for every carbon nucleus in the molecule, on the basis of a comprehensive study of the relevant mono-, di-, tri-, and polysaccharides, including several containing sialic acid (5-acetamido-3, 5-dideoxy-D-glycero-D-galacto-nonulopyranosonic acid), and phospho-, sphingo-, and glycosphingolipids. These assignments represent an extension of the 13C nuclear magnetic resonance data from monosaccharides and lipids to complex oligosaccharides and glycolipids. They also form the basis for interpretation of spectral perturbations induced in GM1 by titration with paramagnetic europium(III). The single sialic acid in GM1 was found to be alpha-glycosidically linked in the oligosaccharide from considerations of its unique anomeric chemical shift. The sialic acid carboxyl and glyceryl side chain, along with additional ligands donated by the 2-acetamido-2-deoxy-beta-D-galactopyranoside and terminal beta-D-galactopyranoside residues in the oligosaccharide portion of GM1, were found to be intimately involved with cation binding. It is proposed that the higher affinity, compared with monomeric sialic acid, of GM1 for cations may result from these additional oligosaccharide groups, which may effectively compete for water ligands in the metal cation coordination sphere.

Lanthanide complexes as fluorescent indicators for neutral sugars and cancer biomarkers

“…Based on these results we conclude, in agreement with Sillerud et al (19), that a sialic acid moiety appended to an oligosaccharide sequence leads to enhanced affinity. Comparison of the fluorescence spectra of 2 in the presence of GM1 with neutral asialo GM1 as well as several other analytes suggests that proximal oligosaccharide-sialic acid sequences are important factors leading to signal transduction (Fig.…”

“…Importantly, Sillerud et al (19) have provided precedent for favorable cooperative binding interactions of the oligosaccharide and sialic acid moieties of micellar gangliosides with Eu 3ϩ . For example, the higher affinity of Eu 3ϩ to GM1 as compared with sialic acid was attributed not only to an electrostatic interaction with the GM1 sialic acid carboxylate but also to secondary interactions with the proximal oligosaccharide hydroxyls, resulting in a coordination shell (Fig.…”

Structure of the capsular polysaccharide antigen of type IV group B Streptococcus

“…This was ascertained by the fact that the more intense signals, usually associated with the more flexible part of the polysaccharide (25), could all be readily assigned to the carbons in the branch consisting of residues (f), (e), and (d) (Fig. 2) virtually identical chemical shifts to the corresponding signals previously assigned (26) to the free trisaccharide a-NeupNAc-…”

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

“…On the other hand, in both GM1 and Ptdlns, the negative charge is "shielded" by a bulky hydrophilic group. In the case of GM1, evidence on head-group conformation indicates that the carboxyl group of the sialic residue and some OH groups of the terminal galactose form an internal chelation complex (45). Therefore, the carboxyl group is oriented toward the terminal galactose residue (46) and may thus be unavailable for interactions with opsonizing proteins.…”