SYNTHESIS AND AGGREGATIVE PROPERTIES OF GM1 GANGLIOSIDE (IV(3)NEU5ACGGOSE(4)CER) CONTAINING D-(-2-HYDROXYSTEARIC ACID())

GM1 ganglioside containing a hydroxylated fatty acid moiety, GM1(OH), was synthesized starting from lyso-GM1 and D-(+)-2-hydroxystearic acid . The aggregative, geometrical and distribution properties of GM1(OH) were compared with those of stearic acid containing GM1 ganglioside; l aser light scattering measurements, differential scanning calorimetry and fluorescence spectroscopy were used. GM1 and GM1(OH) are present i n solution as micelles with a hydrodynamic radius of 58.7 and 60.0 Ang strom, and molecular mass of 470 and 570 kDa, respectively. The surfac e area occupied by the monomer of GM1(OH) at the lipid-water interface of the aggregate was calculated to be 117 Angstrom(2), which is 3 Ang strom(2) lower than that determined for GM1. Proton NMR analyses of GM 1 and GM1(OH) suggest different three-dimensional structures at the ga nglioside lipid-water interface. Both GM1(OH) and GM1 inserted into di palmitoylphosphatidylcholine (DPPC) vesicles undergo segregation pheno mena, with the formation of ganglioside-enriched microdomains, but GM1 (OH) shows a higher degree of dispersion in the DPPC matrix and exerts a lower rigidifying effect than does GM1.