Sonnino S, Acquotti D, Fronza G, Cantù L, Chigorno V, Pitto M, Kirschner G, Tettamanti G
Department of Medical Chemistry and Biochemistry, Medical School, University of Milan, Italy.
Chem Phys Lipids. 1988 Mar;46(3):181-91. doi: 10.1016/0009-3084(88)90020-5.
N-Glycolylneuraminic acid containing GM1, GM1(NeuGc), was prepared by semisynthetic procedure. The procedure makes use of GM1 ganglioside deacetylated at the level of sialic acid residue (deAc-GM1) and of 1,3-dioxalan-2,4-dione. DeAc-GM1 is prepared from GM1 by alkaline hydrolysis in the presence of tetramethylammonium hydroxide and the glycolylating compound by reaction of glycolic acid with phosgene in dioxane, followed by cyclization under vacuum. Mass spectrometric and nuclear magnetic resonance spectroscopy analyses clearly indicated the presence, in the neosynthesized ganglioside of a glycolic group in the sialic acid residue. Laser-light scattering measurements show that GM1(NeuGc) aggregates in aqueous media being present in solution as micelles with a molecular weight of 576,000 and a hydrodynamic radius of 62.4 A as determined at 25 degrees C. GM1(NeuGc) promotes neurite outgrowth in N-2a cells to a similar degree as GM1(NeuAc), but shows different behaviour under treatment with sialidase from Arthrobacter ureafaciens.
含N-羟乙酰神经氨酸的GM1，即GM1(NeuGc)，通过半合成方法制备。该方法利用在唾液酸残基水平脱乙酰化的GM1神经节苷脂（脱乙酰GM1）和1,3-二氧戊环-2,4-二酮。脱乙酰GM1由GM1在氢氧化四甲铵存在下通过碱性水解制备，而羟乙酰化化合物则通过乙醇酸与光气在二氧六环中反应，然后在真空中环化得到。质谱和核磁共振光谱分析清楚地表明，在新合成的神经节苷脂中，唾液酸残基存在一个羟乙酰基。激光散射测量表明，GM1(NeuGc)在水性介质中聚集，在25℃下测定，其在溶液中以分子量为576,000、流体力学半径为62.4 Å的胶束形式存在。GM1(NeuGc)促进N-2a细胞中神经突生长的程度与GM1(NeuAc)相似，但在用脲节杆菌唾液酸酶处理时表现出不同的行为。
