Synthesis of a new nanomolar saccharide inhibitor of lymphocyte adhesion: different polylactosamine backbones present multiple sialyl Lewis x determinants to L-selectin in high-affinity mode

Glycobiology
O RenkonenR Renkonen

Abstract

Lymphocyte infiltration is a hallmark of acute rejections in solid organ transplants, such as cardiac allograft. We have previously shown that lymphocyte extravasation to cardiac grafts undergoing rejection is largely due to interactions between lymphocyte L-selectin and its sialyl Lewis x (sLex) decorated ligands. Our previous work demonstrated further that an enzymatically synthetized tetravalent sLex glycan of a branched polylactosamine backbone is a highly efficient inhibitor of L-selectin-dependent lymphocyte adhesion to graft endothelium. To improve the availability of multivalent sLex glycans for anti-inflammatory indications, we now report enzymatic synthesis of another tetravalent sLex glycan that can be potentially produced on a large scale, and show that even the new saccharide is a nanomolar inhibitor of L-selectin-dependent lymphocyte adhesion. The novel antagonist is sLex beta 1-3' (sLex beta 1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc (8) (where LacNAc is the disaccharide Gal beta 1-4GlcNac and sLex is the tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-4 (Fuc alpha 1-3) GlcNAc). Its five-step synthesis was started from the octameric polylactosamine LacNAc beta 1-3' (GlcNAc beta 1-...Continue Reading

Citations

Aug 7, 2002·The American Journal of Pathology·Jutta RenkonenRisto Renkonen
Aug 29, 2006·Applied and Environmental Microbiology·Yoh-Ichi ShimmaYoshifumi Jigami
Mar 15, 2005·American Journal of Respiratory and Critical Care Medicine·Sanna K Toppila-SalmiRisto L O Renkonen
Oct 20, 2000·Analytical Biochemistry·J RäbinäR Renkonen
Nov 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jens DerneddeRainer Haag
Aug 21, 2007·Biochimica Et Biophysica Acta·Sven EndersRudolf Tauber
May 26, 2004·Chemistry & Biology·Patricia MoweryLaura L Kiessling
Sep 16, 2006·Glycobiology·Bing MaDiane E Taylor
Feb 20, 1999·The Journal of Biological Chemistry·W J SandersL L Kiessling
Jan 29, 1999·Physiological Reviews·D Vestweber, J E Blanks
May 16, 2003·Carbohydrate Research·Fabrice BinteinAndré Lubineau

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