TY - JOUR
T1 - Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands
AU - Bull, Christian
AU - Heise, Torben
AU - Beurskens, Danielle M. H.
AU - Riemersma, Moniek
AU - Ashikov, Angel
AU - Rutjes, Floris P. J. T.
AU - van Kuppevelt, Toin H.
AU - Lefeber, Dirk J.
AU - den Brok, Martijn H.
AU - Adema, Gosse J.
AU - Boltje, Thomas J.
PY - 2015/10
Y1 - 2015/10
N2 - Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells.
AB - Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells.
U2 - 10.1021/acschembio.5b00501
DO - 10.1021/acschembio.5b00501
M3 - Article
C2 - 26258433
VL - 10
SP - 2353
EP - 2363
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 10
ER -