The hexapeptide inhibitor of Galβ1,3GalNAc-specific α2,3-Sialyltransferase as a generic inhibitor of sialyltransferases

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Title
The hexapeptide inhibitor of Galβ1,3GalNAc-specific α2,3-Sialyltransferase as a generic inhibitor of sialyltransferases
Author(s)
Ki-Young Lee; H G Kim; Mi Ran Hwang; Jung Il Chae; J M Yang; Y C Lee; Y K Choo; Young Ik Lee; S S Lee; Su Il Do
Bibliographic Citation
Journal of Biological Chemistry, vol. 277, no. 51, pp. 49341-49351
Publication Year
2002
Abstract
The mammalian Galβ1,3GalNAc-specific α2,3-sialyltransferase (ST3Gal I) was expressed as a secreted glycoprotein in High Five™ (Trichoplusia ni) cells. Using this recombinant ST3Gal I, we screened the synthetic hexapeptide combinatorial library to explore a sialyltransferase inhibitor. We found that the hexapeptide, NH2-GNWWWW, exhibited the most strong inhibition of ST3Gal I among five different hexapeptides that were finally selected. The kinetic analysis of ST3Gal I inhibition demonstrated that this hexapeptide could act as a competitive inhibitor (Ki = 1.1 μm) on CMP-NeuAc binding to the enzyme. Moreover, the hexapeptide was shown to strongly inhibit both N-glycan-specific α2,3and α2,6-sialyltranferase in vitro, suggesting that this peptide may inhibit the broad range of sialyltransferases regardless of their linkage specificity. The inhibitory activity in vivo was investigated by RCA-I lectin blot analyses and by metabolic D-[6-3H]GlcNH2 radiolabeling analyses of N- and O-linked oligosaccharides in Chines hamster ovary cells. Our results demonstrate that the hexapeptide can act as a generic inhibitor of the N- and O-glycan-specific sialyltransferases in mammalian cells, which results in the significantly reduced NeuAc expression on cellular glycoproteins in vivo.
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M209618200
Type
Article
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1. Journal Articles > Journal Articles
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