Strategies for the Synthesis and Screening of Glycoconjugates. 1. A Library of Glycosylamines

Abstract

A simple one-step procedure is found to be highly effective for the "functionalization" of glycodiversity. This study encompasses 50 unprotected mono- and oligosaccharides, which are subjected to Kochetkov aminations in saturated aqueous ammonium carbonate. The reaction allows for the stereo- and regioselective introduction of an amino group into all oligosaccharides tested, as well as into a great variety of monosaccharides including charged species. The resulting unprotected glycosylamines are stable compounds, and the inherent amino group provides a convenient site for chemoselective conjugation and modification as described in the following paper in this issue.

Engineering of protein thermodynamic, kinetic, and colloidal stability: Chemical Glycosylation with monofunctionally activated glycans

“…For the synthesis of SS-mDEX (10 kDa) we followed a strategy previously presented for synthesizing monofunctionally activated small glycans (Vetter and Gallop, 1995). It involves Kochetkov-Lansbury amination (Cohen-Anisfeld and Lansbury, 1993;Likhosherstov et al, 1986) at the single reducing-end glycan of the polysaccharide followed by the attachment of an activated bifunctional succinimidyl linker specific for protein lysine e-amino groups (Supplement Fig.…”

“…In this work we describe: the design of monofunctionally activated polysaccharides (dextran, 10 kDa) to complement previous studies on small glycans (Vetter and Gallop, 1995); the coupling of activated dextran and lactose reagents to the model protein a-chymotrypsin (a-CT) to different extents; the analytical characterization of the bioconjugates; and the employment of the resulting conjugates to systematically study the effects of glycan size and degree of glycosylation on protein thermodynamic, kinetic, and colloidal stability.…”

An Efficient Synthesis of N-Allylglycosylamides from Unprotected Carbohydrates

“…A recent report of a large nunber of mono-and oligosaccharides subjected to the Kochetkov reaction has appeared. 31 There are various drawbacks with these methods. Glycosylamines are not stable compounds.…”

Size-exclusion chromatography of heparin oligosaccharides at high and low pressure

“…This effect was also independent of the nature of the salt, because a combined NaCl/Tris buffer produced similar effects and elution times as displayed for the ammonium bicarbonate buffer (chromatograms not shown). However, an excessive content in ammonium bicarbonate could lead to glycosylamine formation [32] and difficulties in removing ammonium bicarbonate effectively by evaporation. In contrast, the elution time and peak width of the uncharged acetone was not affected by the ionic strength (Fig.…”