Abstract
Glycosylphosphatidylinositol (GPI) anchorage is a common posttranslational modification of eukaryotic proteins. Chemical synthesis of structurally defined GPIs and GPI derivatives is a necessary step toward understanding the properties and functions of these molecules in biological systems. In this work, the synthesis of several functionalized GPI anchors was accomplished using the para-methoxybenzyl (PMB) group for permanent hydroxyl protection, which allowed the incorporation of functionalities that are incompatible with permanent protecting groups traditionally used in carbohydrate synthesis. A flexible convergent-divergent assembly strategy enabled efficient access to a diverse set of target structures, including "clickable" alkyne- and azide-modified GPIs. For global deprotection, a one-pot reaction was employed to afford the target GPIs in excellent yields (85-97%). Fully deprotected clickable GPI derivatives were readily conjugated to imaging and affinity probes via Cu(i)-catalyzed and Cu-free strain-promoted [3 + 2] cycloaddition to result in GPI-Flour and GPI-Biotin conjugates, respectively.
Original language | English |
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Pages (from-to) | 2342-2352 |
Number of pages | 11 |
Journal | Chemical Science |
Volume | 2 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2011 |