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This is an excellent and comprehensive review of the effects of unnatural sialic acids on biological processes such as viral binding and neurite outgrowth.
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Jacobs C.L., Goon S., Yarema K.J., Hinderlich S., Hang H.C., Chai D.H., Bertozzi C.R. Substrate specificity of the sialic acid biosynthetic pathway. Biochemistry. 40:2001;12864-12874.
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This study significantly expands the structural modifications that are possible to engender in cell surface sialic acids. The breakthrough is to bypass the bottleneck step in the pathway, ManNAc 6-kinase, by feeding analogs of sialic acid rather than ManNAc.
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Oetke C., Brossmer R., Mantey L.R., Hinderlich S., Isecke R., Reutter W., Keppler O.T., Pawlita M. Versatile biosynthetic engineering of sialic acid in living cells using synthetic sialic acid analogues. J Biol Chem. 277:2002;6688-6695 This study significantly expands the structural modifications that are possible to engender in cell surface sialic acids. The breakthrough is to bypass the bottleneck step in the pathway, ManNAc 6-kinase, by feeding analogs of sialic acid rather than ManNAc.
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Schilling B., Goon S., Samuels N.M., Gaucher S.P., Leary J.A., Bertozzi C.R., Gibson B.W. Biosynthesis of sialylated lipooligosaccharides in Haemophilis ducreyi is dependent on exogenous sialic acid and not mannosamine. Incorporation studies using N-acylmannosamine analogues, N-glycolylneuraminic acid, and C-13-labeled N-acetylneuraminic acid. Biochemistry. 40:2001;12666-12677.
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This is the first example of biosynthetic modulation of sialic acid in bacteria.
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Goon S., Schilling B., Tullius M.V., Gibson B.W., Bertozzi C.R. Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides. Proc Natl Acad Sci USA. 100:2003;3089-3094 This is the first example of biosynthetic modulation of sialic acid in bacteria.
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Goon, S.1
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22
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This paper demonstrates that PSA can be selectively disrupted by a metabolic inhibitor, ManNBut, without detectable effects on the expression of other forms of sialic acid. This offers a tool to study the functions of PSA in vivo.
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Mahal L.K., Charter N.W., Angata K., Fukuda M., Koshland D.E. Jr., Bertozzi C.R. A small-molecule modulator of poly-α-2,8-sialic acid expression on cultured neurons and tumor cells. Science. 294:2001;380-382 This paper demonstrates that PSA can be selectively disrupted by a metabolic inhibitor, ManNBut, without detectable effects on the expression of other forms of sialic acid. This offers a tool to study the functions of PSA in vivo.
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Charter N.W., Mahal L.K., Koshland D.E. Jr., Bertozzi C.R. Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior. J Biol Chem. 277:2002;9255-9261.
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Hang H.C., Bertozzi C.R. Chemoselective approaches to glycoprotein assembly. Acc Chem Res. 34:2001;727-736.
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Mahal L.K., Yarema K.J., Bertozzi C.R. Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. Science. 276:1997;1125-1128.
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Metabolic delivery of ketone groups to sialic acid residues - Application to cell surface glycoform engineering
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Yarema K.J., Mahal L.K., Bruehl R.E., Rodriguez E.C., Bertozzi C.R. Metabolic delivery of ketone groups to sialic acid residues - application to cell surface glycoform engineering. J Biol Chem. 273:1998;31168-31179.
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Yarema, K.J.1
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28
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This paper demonstrates that the GalNAc salvage pathway can be exploited for metabolic oligosaccharide engineering.
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Hang H.C., Bertozzi C.R. Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface engineering. J Am Chem Soc. 123:2001;1242-1243 This paper demonstrates that the GalNAc salvage pathway can be exploited for metabolic oligosaccharide engineering.
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29
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Cell-wall engineering of living bacteria
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This is the first report of the introduction of bio-orthogonal functional groups into bacterial cell walls using biosynthetic mechanisms. The work may have applications in vaccine development or cell targeting.
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Sadamoto R., Niikura K., Sears P.S., Liu H.T., Wong C.H., Suksomcheep A., Tomita F., Monde K., Nishimura S.I. Cell-wall engineering of living bacteria. J Am Chem Soc. 124:2002;9018-9019 This is the first report of the introduction of bio-orthogonal functional groups into bacterial cell walls using biosynthetic mechanisms. The work may have applications in vaccine development or cell targeting.
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Nishimura, S.I.9
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30
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This paper introduces the Staudinger ligation as a novel chemistry for cell surface modification.
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Saxon E., Bertozzi C.R. Cell surface engineering by a modified Staudinger reaction. Science. 287:2000;2007-2010 This paper introduces the Staudinger ligation as a novel chemistry for cell surface modification.
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31
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Saxon E., Luchansky S.J., Hang H.C., Yu C., Lee S.C., Bertozzi C.R. Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation. J Am Chem Soc. 124:2002;14893-14902.
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32
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This paper demonstrates that the GlcNAc salvage pathway is tolerant of unnatural azido-GlcNAc analogs, resulting in their incorporation into O-GlcNAc-modified proteins. This provides a means to selectively tag the modified proteins for proteomics analysis.
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Vocadlo D.J., Hang H.C., Kim E.-J., Hanover J.A., Bertozzi C.R. A chemical approach for identifying O-GlcNAc modified proteins in cells. Proc Natl Acad Sci USA. 100:2003;9116-9121 This paper demonstrates that the GlcNAc salvage pathway is tolerant of unnatural azido-GlcNAc analogs, resulting in their incorporation into O-GlcNAc-modified proteins. This provides a means to selectively tag the modified proteins for proteomics analysis.
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Inoue Y, Lee YC, Troy FA III, Eds. Osaka, Japan: Gakushin Publishing Company
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Mahal, L.K.1
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Exploiting differences in sialoside expression for selective targeting of MRI contrast reagents
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Lemieux G.A., Yarema K.J., Jacobs C.L., Bertozzi C.R. Exploiting differences in sialoside expression for selective targeting of MRI contrast reagents. J Am Chem Soc. 121:1999;4278-4279.
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Kinetic parameters for small-molecule drug delivery by covalent cell surface targetting
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Nauman D.A., Bertozzi C.R. Kinetic parameters for small-molecule drug delivery by covalent cell surface targetting. Biochim Biophys Acta. 1568:2001;147-154.
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40
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This is the first report on the use of unnatural sialic acid biosynthesis for tumor immunotherapy. The results suggest that unnatural mannosamine precursors are converted to sialic acids in animals and incorporated into cell surface glycans. In addition, the work demonstrates that the immune system can discriminate between natural glycans and their subtly modified variants induced by metabolic engineering.
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Liu T.M., Guo Z.W., Yang Q.L., Sad S., Jennings H.J. Biochemical engineering of surface alpha 2-8 polysialic acid for immunotargeting tumor cells. J Biol Chem. 275:2000;32832-32836 This is the first report on the use of unnatural sialic acid biosynthesis for tumor immunotherapy. The results suggest that unnatural mannosamine precursors are converted to sialic acids in animals and incorporated into cell surface glycans. In addition, the work demonstrates that the immune system can discriminate between natural glycans and their subtly modified variants induced by metabolic engineering.
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J Biol Chem
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Liu, T.M.1
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41
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0035072647
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Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens
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Lemieux G.A., Bertozzi C.R. Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens. Chem Biol. 8:2001;265-275.
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0035006049
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This work uses metabolic oligosaccharide engineering as a tool to select for genetic defects that affect sialic acid metabolism. Mutant cell populations with defects in UDP-GlcNAc 2-epimerase were identified that share phenotypic qualities with cells from sialuria patients. The genetic mutations in both were found to be identical.
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Yarema K.J., Goon S., Bertozzi C.R. Metabolic selection of glycosylation defects in human cells. Nat Biotechnol. 19:2001;553-558 This work uses metabolic oligosaccharide engineering as a tool to select for genetic defects that affect sialic acid metabolism. Mutant cell populations with defects in UDP-GlcNAc 2-epimerase were identified that share phenotypic qualities with cells from sialuria patients. The genetic mutations in both were found to be identical.
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Nat Biotechnol
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Yarema, K.J.1
Goon, S.2
Bertozzi, C.R.3
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43
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0033591388
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UDP-GlcNAc 2-epimerase: A regulator of cell surface sialylation
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This paper confirmed a primary role for UDP-GlcNAc 2-epimerase in the biosynthesis of sialic acid.
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Keppler O.T., Hinderlich S., Langner J., Schwartz-Albiez R., Reutter W., Pawlita M. UDP-GlcNAc 2-epimerase: a regulator of cell surface sialylation. Science. 284:1999;1372-1376 This paper confirmed a primary role for UDP-GlcNAc 2-epimerase in the biosynthesis of sialic acid.
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(1999)
Science
, vol.284
, pp. 1372-1376
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Keppler, O.T.1
Hinderlich, S.2
Langner, J.3
Schwartz-Albiez, R.4
Reutter, W.5
Pawlita, M.6
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44
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0037424247
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GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism
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Metabolic oligosaccharide biosynthesis was used to probe the function of GlcNAc 2-epimerase. The work demonstrated that GlcNAc 2-epimerase serves a catabolic role in sialic acid metabolism, a purpose opposite to that of UDP-GlcNAc 2-epimerase.
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Luchansky S.J., Yarema K.J., Takahashi S., Bertozzi C.R. GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism. J Biol Chem. 278:2003;8035-8042 Metabolic oligosaccharide biosynthesis was used to probe the function of GlcNAc 2-epimerase. The work demonstrated that GlcNAc 2-epimerase serves a catabolic role in sialic acid metabolism, a purpose opposite to that of UDP-GlcNAc 2-epimerase.
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(2003)
J Biol Chem
, vol.278
, pp. 8035-8042
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Luchansky, S.J.1
Yarema, K.J.2
Takahashi, S.3
Bertozzi, C.R.4
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45
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0037099395
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A stepwise Huisgen cycloaddition process: Copper(I)-catalyzed regioselective 'ligation' of azides and terminal alkynes
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This report describes the development of a copper(I)-catalyzed 1,3-dipolar cycloaddition between azides and alkynes that proceeds readily under physiological conditions.
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Rostovtsev V.V., Green L.G., Fokin V.V., Sharpless K.B. A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective 'ligation' of azides and terminal alkynes. Angew Chem Int Ed Engl. 41:2002;2596-2599 This report describes the development of a copper(I)-catalyzed 1,3-dipolar cycloaddition between azides and alkynes that proceeds readily under physiological conditions.
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(2002)
Angew Chem Int Ed Engl
, vol.41
, pp. 2596-2599
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Rostovtsev, V.V.1
Green, L.G.2
Fokin, V.V.3
Sharpless, K.B.4
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46
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0037462106
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Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3+2] cyloaddition
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The authors utilized the titular reaction between azides and alkynes to tag azide-labeled proteins from tissue extracts. The technique was used for functional proteomics analysis with mechanism-based covalent inhibitors.
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Speers A.E., Adam G.C., Cravatt B.F. Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3+2] cyloaddition. J Am Chem Soc. 125:2003;4686-4687 The authors utilized the titular reaction between azides and alkynes to tag azide-labeled proteins from tissue extracts. The technique was used for functional proteomics analysis with mechanism-based covalent inhibitors.
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(2003)
J Am Chem Soc
, vol.125
, pp. 4686-4687
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Speers, A.E.1
Adam, G.C.2
Cravatt, B.F.3
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