HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 51, 49341-49351, December 20, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/51/49341    most recent M209618200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, K.-Y. Articles by Do, S.-I. Search for Related Content PubMed PubMed Citation Articles by Lee, K.-Y. Articles by Do, S.-I. Social Bookmarking                      What's this?

The Hexapeptide Inhibitor of Gal1,3GalNAc-specific 2,3-Sialyltransferase as a Generic Inhibitor of Sialyltransferases^*

Ki-Young Lee, Hyung Gu Kim^§, Mi Ran Hwang, Jung Il Chae, Jai Myung Yang^§, Young Choon Lee^¶, Young Kug Choo, Young Ik Lee^**, Sang-Soo Lee, and Su-Il Do^§§

From the  Animal Cell and Medical Glycobiology Laboratory and ^** Liver Cell Signal Transduction Laboratory, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusung, Taejon 305-333, South Korea, the ^§ Department of Life Science, Sogang University, Seoul 100-601, South Korea, the ^¶ Division of Natural Resources and Life Science, Dong-A University, Busan 604-022, South Korea, the  Division of Biological Science, WonKwang University, Iksan 570-749, South Korea, and the  Department of Biochemistry, Pai Chai University, Taejon 302-735, South Korea

The mammalian Gal1,3GalNAc-specific 2,3-sialyltransferase (ST3Gal I) was expressed as a secreted glycoprotein in High Five^TM (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 (K_i = 1.1 µM) on CMP-NeuAc binding to the enzyme. Moreover, the hexapeptide was shown to strongly inhibit both N-glycan-specific 2,3- and 2,6-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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Perez-Vilar, R. Mabolo, C. T. McVaugh, C. R. Bertozzi, and R. C. Boucher Mucin Granule Intraluminal Organization in Living Mucous/Goblet Cells: ROLES OF PROTEIN POST-TRANSLATIONAL MODIFICATIONS AND SECRETION J. Biol. Chem., February 24, 2006; 281(8): 4844 - 4855. [Abstract] [Full Text] [PDF]