The conformational properties of the gangliosides G_M2 and G_M1 based on ¹H and,¹³C nuclear magnetic resonance studies

Abstract

A comparison of the 1 H and 13 C nmr parameters for the disaccharide derivatives βDGal(1→ 4)βDGlcO(CH 2 ) 8 COOCH 3 (1), βDGalNAc(1 → 4)βDGalO(CH 2 ) 8 COOCH 3 (2), and βDGal(1 → 3)βDGalNAcO(CH 2 ) 2 CH 3 (3) allowed assignments of the signals observed for the asialo-G M2 - and asialo-G M1 -related synthetic haptens, βDGalNAc(1 → 4)βDGal(1→4)βDGlcO(CH 2 ) 8 COOCH 3 (4) and βDGal(1 → 3)βDGalNAc(1 → 4)βDGal(1 → 4)βDGlcO(CH 2 ) 8 COOCH 3 (5). 1 H nuclear Overhauser enhancement studies confirmed the conformational preferences for 2 and 3 predicted by HSEA calculation. Comparison of the 1 H and 13 C spectra indicate that these preferences and that previously known for the lactoside (1) are closely maintained in the haptens 4 and 5. HSEA calculation indicates that the methyl group of methyl N-acetyl-α-D-neuraminic acid (10) prefers the orientation wherein the carboxyl group is near anti-periplanar to the methyl group. However, this orientation was not confirmed by saturation of the methyl group since no enhancement of either Ha-3 or He-3 was observed. On the other hand, saturation of Ha-3 c of the αDNeuAc unit of the G M1 -related pentasaccharide, βDGal(1 → 3)βDGalNAc(1 → 4)[αDNeuAc(2 → 3)]βDGal(1→4)α,βDGlc, caused strong enhancement of the signal for the aglyconic hydrogen, H-3 b of the βDGal(1→4) unit. This observation, along with those of other nuclear Overhauser experiments, established that this pentasaccharide has the carboxyl group anti-periplanar to C-3 b . Furthermore, the C-7 c to C-9 c chain of the αDNeuAc unit adopts nearly the same conformation for the compound in aqueous solution as exists for N-acetylneuraminic acid in the crystalline state. The HSEA calculation indicates important attractive interaction between this chain and the βDGalNAc unit of the aglycon. These conlcusions were extended to the G M2 and G M1 gangliosides by the comparison of chemical shift data. In these compounds, the carboxyl group projects over the hydrophobic α-side of the βDGalNAc unit and the polar OH-4 c , NAc-5 c , OH-7 c groups project over the hydrophobic β-side of the lactose unit. Comments are made on the possible bearing of these topographical features on certain biological properties of gangliosides.