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

J. Biol. Chem., Vol. 279, Issue 40, 42345-42349, October 1, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/40/42345    most recent M402744200v2 M402744200v1 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 Jing, W. Articles by DeAngelis, P. L. Search for Related Content PubMed PubMed Citation Articles by Jing, W. Articles by DeAngelis, P. L. Social Bookmarking                      What's this?

Synchronized Chemoenzymatic Synthesis of Monodisperse Hyaluronan Polymers^*

Wei Jing and Paul L. DeAngelis¶

From the Hyalose LLC, Oklahoma City, Oklahoma 73104 and the Department of Biochemistry and Molecular Biology, Oklahoma Center for Medical Glycobiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104

The length of the hyaluronan (HA) polysaccharide chain dictates its biological effects in many cellular and tissue systems. Long and short HA polymers often appear to have antagonistic or inverse effects. However, no source of very defined, uniform HA polymers with sizes greater than 10 kDa is currently available. We present a method to produce synthetic HA with very narrow size distributions in the range of 16 kDa to 2 MDa. The Pasteurella HA synthase enzyme, pmHAS, catalyzes the synthesis of HA polymer utilizing monosaccharides from UDP-sugar precursors. Recombinant pmHAS will also elongate exogenously supplied HA oligosaccharide acceptors in vitro in a nonprocessive fashion. As a result of bypassing the slow initiation step in vitro, the elongation process is synchronized in the presence of acceptor; thus all of polymer products are very similar in length. In contrast, without the use of an acceptor, the final polymer size range is difficult to predict and the products are more polydisperse. HA polymers of a desired size are constructed by controlling the reaction stoichiometry (i.e. molar ratio of precursors and acceptor molecules). The use of modified acceptors allows the synthesis of HA polymers containing tags (e.g. fluorescent, radioactive). In this scheme, each molecule has a single foreign moiety at the reducing terminus. Alternatively, the use of radioactive UDP-sugar precursors allows the synthesis of uniformly labeled native HA polymers. Overall, synthetic HA reagents with monodisperse size distributions and defined structures should assist in the elucidation of the numerous roles of HA in health and disease.

Received for publication, March 11, 2004 , and in revised form, August 4, 2004.

^* This work was supported in part by grants from the National Science Foundation (MCB-9876193) and the Oklahoma Center for Advancement of Science and Technology (Oklahoma Applied Research Support AR022–019) (to P. L. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 405-271-2227; Fax: 405-271-3092; E-mail: paul-deangelis{at}ouhsc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. H. Weigel and P. L. DeAngelis Hyaluronan Synthases: A Decade-plus of Novel Glycosyltransferases J. Biol. Chem., December 21, 2007; 282(51): 36777 - 36781. [Abstract] [Full Text] [PDF]

				A. E. Sismey-Ragatz, D. E. Green, N. J. Otto, M. Rejzek, R. A. Field, and P. L. DeAngelis Chemoenzymatic Synthesis with Distinct Pasteurella Heparosan Synthases: MONODISPERSE POLYMERS AND UNNATURAL STRUCTURES J. Biol. Chem., September 28, 2007; 282(39): 28321 - 28327. [Abstract] [Full Text] [PDF]

				J. Vionnet and W. F Vann Successive glycosyltransfer of sialic acid by Escherichia coli K92 polysialyltransferase in elongation of oligosialic acceptors Glycobiology, July 1, 2007; 17(7): 735 - 743. [Abstract] [Full Text] [PDF]

				B. S. Tracy, F. Y. Avci, R. J. Linhardt, and P. L. DeAngelis Acceptor Specificity of the Pasteurella Hyaluronan and Chondroitin Synthases and Production of Chimeric Glycosaminoglycans J. Biol. Chem., January 5, 2007; 282(1): 337 - 344. [Abstract] [Full Text] [PDF]

				K. J. Williams, K. M. Halkes, J. P. Kamerling, and P. L. DeAngelis Critical Elements of Oligosaccharide Acceptor Substrates for the Pasteurella multocida Hyaluronan Synthase J. Biol. Chem., March 3, 2006; 281(9): 5391 - 5397. [Abstract] [Full Text] [PDF]