GEOMETRICAL AND CONFORMATIONAL PROPERTIES OF GANGLIOSIDE GALNAC-G(D1A), IV(4)GALNACIV(3)NEU5ACII(3)NEU5ACGGOSE(4)CER

The aggregative properties of GalNAc-G(D1a) ganglioside, in comparison with those of G(D1a), have been investigated and correlated to the in trinsic conformation and mobility of the oligosaccharide chain of the molecules. Micellar parameters in aqueous solution (molecular mass, hy drodynamic radius as well as the surface area at the lipid/water inter face and the packing parameter of the monomer inserted in the aggregat e) are measured by the laser light-scattering technique. The presence of a further GalNAc residue causes a 22% increase in molecular mass, c ontrary to expectation. Oligosaccharide moiety three-dimensional struc tures have been modeled using molecular mechanics and dynamics calcula tions, based on NOE interactions observed for native gangliosides diss olved in deuterated dimethylsulfoxide or, as mixed micelles with fully deuterated dodecylphosphocholine, in D2O. Compared with G(D1A) the Ga lNAc-G(D1a) is less mobile, thus influencing the surface area, this lo wer mobility together with the GalNAc-G(D1a) conformation leads to a l arger number of monomers participating in the formation of the micelle . The results further substantiate the model in which the three-dimens ional structure and the intrinsic dynamic properties of the oligosacch aride chain affect the geometrical properties of the aggregate.