New structural insights into the oligosaccharide phosphate fraction of Pichia (Hansenula) holstii NRRL Y2448 phosphomannan

作者：Handley Paul N^*; Carroll Anthony; Ferro Vito^*

来源：Carbohydrate Research, 2017, 446: 68-75.

DOI：10.1016/j.carres.2017.05.008

• Oligosaccharides
• Structure elucidation
• NMR spectroscopy
• PI-88

The oligosaccharide phosphate fraction (OPF) obtained from mild acid hydrolysis of P. holstii NRRLY-2448 phosphomannan is the starting material for the preparation of the Phase III anticancer drug candidate PI 88. The OPF was for the first time successfully separated by preparative ion exchange chromatography and the major oligosaccharides isolated and characterized by NMR spectroscopy. The components were also acetylated and subjected to LC-MS analysis. These studies revealed that the OPF also contained all alpha(1 -> 3)-linked oligosaccharides in addition to the known alpha(1 -> 3)/(1 -> 2)-linked species, most likely formed by hydrolysis of the latter. Contrary to previous assumptions, the only phosphorylated disaccharide present is alpha(1 -> 3)-linked. In addition, it was determined that a glycosylamine derivative previously isolated is, in fact, a manufacturing byproduct formed from exposure to aqueous ammonium bicarbonate during chromatographic purification. Based on these findings a new generic structure for PI 88 is proposed which more accurately reflects its composition.

• 出版日期2017-6-29