Abstract
Glycobiology has made very significant progress in the past: decades. However, further progress will significantly depend on the establishment of novel methods for miniaturized, high-throughput analysis of glycan-protein interactions. Robust: solid-phase chemical tools and new, chemoselective reagents for biologically meaningful display of surface-immobilized glycans are likely to play a key role. Here we present four new bifunctional linkers that allow highly chemoselective capture of unprotected glycans in solution to form glycan-linker conjugates for direct construction of glycan microarrays (glycochips). The bifunctional linkere carry O-liriked aminooxy moieties, some with N-substituents at one end and an amino group at the other. In addition, they contain a substituted benzene ring for UV traceability and improved pari-fication of glycan-linker conjugates. NMR spectroscopic studies in solution proved that N-substituted amlnooxy linkers provided model glycan-linker conjugates with the β-glucopyranoside configuration, i. e. the ring-closed form required for biological, recognition. Then an ensemble of glycan-linker conjugates were assembled from mannobiose, lactose, and N-acetyl-lactosamine and used for covalent printing of glycan microarrays. The stability of oximes were studied both in solution and on-chip. In solution, two of the linkers provided glycan-linker conjugates with a remarkable stability at pH 4 or higher, on-chip this relative stability was upheld. Two of the linkers, with different properties, are recommended for the glycobiology toolbox for the construction of glycan microarrays from unprotected glycans.
| Original language | English |
|---|---|
| Journal | European Journal of Organic Chemistry |
| Volume | 2010 |
| Issue number | 3 |
| Pages (from-to) | 540-554 |
| Number of pages | 15 |
| ISSN | 1434-193X |
| DOIs | |
| Publication status | Published - 2010 |