Peng (George) Wang
Research Interests:
The focus of Professor Wang’s research is on synthetic organic chemistry,
bioorganic chemistry and biochemistry. Combining modern organic synthesis
with the latest discoveries in biology, we have been undertaking research
programs on natural product synthesis, on reactive nitrogen species,
on synthetic methodology development, and on biosynthetic pathway engineering.
Our total synthesis of natural products especially biomedically important
products containing carbohydrates relies on the use of novel organic
transformation (such as new orgometallic reagents) and of enzymatic
synthesis. One large class of natural products of interests is carbohydrate-containing
structures involved in human immunology. One such sequence is two galactoses
linked by alpha 1,3-glycosidic bond (called a-Gal epitope) which is
involved in hyperacute rejection in animal-to-human xenotransplantation.
We hope that our work on the synthesis of a-Gal-containing glycoconjugates
including a-Gal epitopes, its multivalent derivatives and a-Gal sugar
mimetic libraries through combinatorial strategies will result in broad
biomedical applications.
Another of our current targets is saccharomicins, a new class of antibiotics
that contains 17 uncommon monosaccharide units. Its total synthesis
involves development of feasible synthetic strategies for constructing
a variety of uncommon sugars and for stereospecifically linking two
hindered sugars together.
Reactive nitrogen species such as nitric oxide (NO) and peroxynitrite
play important roles in numerous physiological and pathophysiological
processes. Our research focus in this area is to design and synthesize
a variety of NO donor compounds which can deliver NO at the specific
time and place to evoke biological functions. One class of such novel
NO donors is sugar-NO-donor conjugates. Our working hypothesis is that
the sugar-NO conjugates will be accumulated by tumor cells according
to the distribution of sugar transporter proteins so that greater cytotoxicity
and modulating activity will be achieved. We also design and synthesize
inhibitors for cysteine-dependent enzymes such as proteases and proten-tyrosine-phosphatases
based on NO-mediated S-nitrosation mechanism.
Recently we have initiated a genome-based program aiming at producing
a variety of complex natural products through fermentation of bioengineered
microorganisms. The research first involves finding and cloning of each
individual enzyme from various genomic databases along the biosynthetic
pathway of a natural product such as an important carbohydrate structure.
Then the genes of all necessary biosynthetic enzymes are reassembled
into a gene cluster. This natural product biosynthetic gene cluster
is transformed into E. coli to make a “superbug” which can
produce the natural product and its derivatives cost effectively through
fermentation.
Publications
Selected publications from the last 5 years:
Li R, Chen Q, Wang, P. G., Qi Q. (2007) "A novel-designed Escherichia coli for the production of various polyhydroxyalkanoates from inexpensive substrate mixture." Appl Microbiol Biotechnol [Epub ahead of print]
Shen Z, Huang M, Xiao C, Zhang Y, Zeng X, Wang, P. G.. (2007) "Nonlabeled Quartz Crystal Microbalance Biosensor for Bacterial Detection Using Carbohydrate and Lectin Recognitions." Anal Chem [Epub ahead of print]
Wang S, Wang, P. G., Qi Q. (2007) "Influence of substrate conformation on the deglycosylation of ribonuclease B by recombinant yeast peptide:N-glycanase." Acta Biochim Biophys Sin (Shanghai) 39(1), 8-14.
Huang GL, Mei XY, Zhang HC, Wang, P. G.. (2006) "A new fermentation process allows large-scale production of tetra-N-acetyl-chitotetraosyl allosamizoline." J Enzyme Inhib Med Chem 21(5), 597-9.
Huang GL, Mei XY, Zhang HX, Wang, P. G.. (2006) "Fabrication and application of carbohydrate microarray for analyzing human serum antibody-carbohydrate interaction." Appl Microbiol Biotechnol [Epub ahead of print]
Xia C, Zhou D, Liu C, Lou Y, Yao Q, Zhang W, Wang, P. G.. (2006) "Thio-isoglobotrihexosylceramide, an agonist for activating invariant natural killer T cells." Org Lett. 8(24), 5493-6.
Guo H, Li L, Wang, P. G.. (2006) "Biochemical characterization of UDP-GlcNAc/Glc 4-epimerase from Escherichia coli O86:B7." Biochemistry 45(46), 13760-8.
Zhang Y, Yao Q, Xia C, Jiang X, Wang, P. G.. (2006) "Trapping norovirus by glycosylated hydrogels: a potential oral antiviral drug." Chem Med Chem 1(12), 1361-6.
Fang L, Battisti RF, Cheng H, Reigan P, Xin Y, Shen J, Ross D, Chan KK, Martin EW Jr, Wang, P. G., Sun D. (2006) "Enzyme specific activation of benzoquinone ansamycin prodrugs using HuCC49DeltaCH2-beta-galactosidase conjugates." J Med Chem 49(21), 6290-7.
Zhang HC, Bi JY, Chen C, Huang GL, Qi QS, Xiao M, Wang, P. G.. (2006) "Immobilization of UDP-galactose 4-epimerase from Escherichia coli on the yeast cell surface." Biosci Biotechnol Biochem 70(9), 2303-6.
Nahalka J, Gemeiner P, Bucko M, Wang, P. G.. (2006) "Bioenergy beads: a tool for regeneration of ATP/NTP in biocatalytic synthesis." Artif Cells Blood Substit Immobil Biotechnol 34(5), 515-21.
Yi W, Zhu L, Guo H, Li M, Li J, Wang, P. G.. (2006) "Formation of a new O-polysaccharide in Escherichia coli O86 via disruption of a glycosyltransferase gene involved in O-unit assembly." Carbohydr Res 341(13), 2254-60.
Huang GL, Mei XY, Wang, P. G.. (2006) "Interactions of carbohydrates and proteins by fluorophore-assisted carbohydrate electrophoresis." J Biosci 31(2), 219-22.
Chen C, Shi Y, Li S, Qi Q, Gu L, Song J, Wang, P. G.. (2006) "A glycosylated nitric oxide donor, beta-Gal-NONOate, and its site-specific antitumor activity." Arch Pharm (Weinheim) 339(7), 366-71.
Chen C, Shi YQ, Song J, Qi QS, Gu L, Wang, P. G.. (2006) "Delivery of Nitric Oxide Released from beta-Gal-NONOate Activation by beta-Galactosidase and Its Activity against Escherichia coli." Biol Pharm Bull 29(6), 1239-41.
Huang GL, Huang HL, Zhang HC, Wang, P. G.. (2006) "Structure-function relations of carbohydrates by neoglycolipid arrays." Appl Biochem Biotechnol 133(3), 211-6.
Yi W, Yao Q, Zhang Y, Motari E, Lin S, Wang, P. G.. (2006) "The wbnH gene of Escherichia coli O86:H2 encodes an alpha-1,3-N-acetylgalactosaminyl transferase involved in the O-repeating unit biosynthesis." Biochem Biophys Res Commun 344(2), 631-9.
Guo H, Lokko K, Zhang Y, Yi W, Wu Z, Wang, P. G.. (2006) "Overexpression and characterization of Wzz of Escherichia coli O86:H2." Protein Expr Purif 48(1), 49-55.
Zhang C, Albermann C, Fu X, Peters NR, Chisholm JD, Zhang G, Gilbert EJ, Wang, P. G., Van Vranken DL, Thorson JS. (2006) "RebG- and RebM-catalyzed indolocarbazole diversification." Chembiochem 7(5), 795-804.
Huang GL, Mei XY, Zhang HC, Wang, P. G.. (2006) "Chemo-enzymatic synthesis of tetra-N-acetyl-chitotetraosyl allosamizoline." Bioorg Med Chem Lett 16(11), 2860-1.
Zhang Y, Luo S, Tang Y, Yu L, Hou KY, Cheng JP, Zeng X, Wang, P. G.. (2006) "Carbohydrate-protein interactions by "clicked" carbohydrate self-assembled monolayers." Anal Chem 78(6), 2001-8.
Wang Z, Qi Q, Wang, P. G.. (2006) "Engineering of cyclodextrin glucanotransferase on the cell surface of Saccharomyces cerevisiae for improved cyclodextrin production." Appl Environ Microbiol 72(3), 1873-7.
Zhang G, Fang L, Zhu L, Zhong Y, Wang, P. G., Sun D. (2006) "Syntheses and biological activities of 3'-azido disaccharide analogues of daunorubicin against drug-resistant leukemia." J Med Chem 49(5), 1792-9.
Yao Q, Song J, Xia C, Zhang W, Wang, P. G.. (2006) "Chemoenzymatic syntheses of iGb3 and Gb3." Org Lett 8(5), 911-4
Xia C, Yao Q, Schumann J, Rossy E, Chen W, Zhu L, Zhang W, De Libero G, Wang, P. G.. (2006) "Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3)." Bioorg Med Chem Lett 16(8), 2195-9.
Fang L, Zhang G, Li C, Zheng X, Zhu L, Xiao JJ, Szakacs G, Nadas J, Chan KK, Wang, P. G., Sun D. (2006) "Discovery of a daunorubicin analogue that exhibits potent antitumor activity and overcomes P-gp-mediated drug resistance." J Med Chem 49(3), 932-41.
Huang GL, Zhang HC, Wang, P. G.. (2006) "Fabrication and application of neoglycolipid arrays in a microtiter plate." Bioorg Med Chem Lett 16(7), 2031-3.
Huang GL, Zhang DW, Zhao HJ, Zhang HC, Wang, P. G.. (2006) "Chemo-enzymatic synthesis of allyl penta-N-acetyl-chitopentaose." Bioorg Med Chem Lett 16(7), 2042-3.
Ryu K, Lin S, Shao J, Song J, Chen M, Wang W, Li H, Yi W, Wang, P. G.. (2005) "Synthesis of complex carbohydrates and glyconjugates: enzymatic synthesis of globotetraose using alpha-1,3-N-acetylgalactosaminyltransferase LgtD from Haemophilus infuenzae strain Rd." Methods Mol Biol 310, 93-105.
Guo H, Yi W, Shao J, Lu Y, Zhang W, Song J, Wang, P. G..(2005) "Molecular analysis of the O-antigen gene cluster of Escherichia coli O86:B7 and characterization of the chain length determinant gene (wzz)." Appl Environ Microbiol 71(12), 7995-8001.
Huang GL, Zhang DW, Zhao HJ, Zhang HC, Wang, P. G.. (2005) "Chemo-enzymatic synthesis of 1,4-oxazepanyl sugar as potent inhibitor of chitinase." Bioorg Med Chem 14(7), 2446-9.
Yi W, Bystricky P, Yao Q, Guo H, Zhu L, Li H, Shen J, Li M, Ganguly S, Bush CA, Wang, P. G..(2005) "Two different O-polysaccharides from Escherichia coli O86 are produced by different polymerization of the same O-repeating unit."
Carbohydr Res ;341(1), 100-8.
Yang S, Gao M, Cui Y, Yan KL, Ren YQ, Zhang GL, Wang, P. G., Xiao FL, Du WH, Liang YH, Sun LD, Xu SJ, Huang W, Zhang XJ.(2005) "Identification of a novel locus for Marie Unna hereditary hypotrichosis to a 17.5 cM interval at 1p21.1-1q21.3."
J Invest Dermatol 125(4), 711-4.
Zhang G, Fang L, Zhu L, Sun D, Wang, P. G.. (2005) "Syntheses and biological activity of bisdaunorubicins."
Bioorg Med Chem ;14(2), 426-34. Epub 2005 Sep 22.
Cai TB, Lu D, Wang, P. G.. (2005) "N-hydroxyguanidines as substrates of nitric oxide synthases.
Curr Top Med Chem 5(7), 721-36. Review. "
Zhang G, Fang L, Zhu L, Aimiuwu JE, Shen J, Cheng H, Muller MT, Lee GE, Sun D, Wang, P. G.. (2005) "Syntheses and biological activities of disaccharide daunorubicins."
J Med Chem 48(16), 5269-78.
Zhu L, Cao X, Chen W, Zhang G, Sun D, Wang, P. G.. (2005) "Syntheses and biological activities of daunorubicin analogs with uncommon sugars."
Bioorg Med Chem 13(23), 6381-7.
Eguchi H, Ikeda Y, Ookawara T, Koyota S, Fujiwara N, Honke K, Wang, P. G., Taniguchi N, Suzuki K.(2005) "Modification of oligosaccharides by reactive oxygen species decreases sialyl lewis x-mediated cell adhesion."
Glycobiology ;15(11), 1094-101.
Wei L, Wei G, Zhang H, Wang, P. G., Du Y.(2005) "Synthesis of new, potent avermectin-like insecticidal agents."
Carbohydr Res 340(9), 1583-90.
Huang GL, Zhang HC, Wang, P. G.. (2005) "Hydrolysis characteristics of a beta-1,3-D-glucan elicitor from yeast."
Biotechnol Appl Biochem 42(Pt 3), 219-22.
Cai TB, Lu D, Tang X, Zhang Y, Landerholm M, Wang, P. G.. (2005) "New glycosidase activated nitric oxide donors: glycose and 3-morphorlinosydnonimine conjugates."
J Org Chem 70(9), 3518-24.
Wang, P. G., Wei J, Chang M, El-Shourbagy T.(2005) "High-throughput determination of atrasentan in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry."
Biomed Chromatogr 19(9), 663-70.
Zhang G, Shen J, Cheng H, Zhu L, Fang L, Luo S, Muller MT, Lee GE, Wei L, Du Y, Sun D, Wang, P. G.. (2005) "Syntheses and biological activities of rebeccamycin analogues with uncommon sugars."
J Med Chem 48(7), 2600-11.
Yi W, Shao J, Zhu L, Li M, Singh M, Lu Y, Lin S, Li H, Ryu K, Shen J, Guo H, Yao Q, Bush CA, Wang, P. G.. (2005) "Escherichia coli O86 O-antigen biosynthetic gene cluster and stepwise enzymatic synthesis of human blood group B antigen tetrasaccharide."
J Am Chem Soc 127(7), 2040-1.
Cheng H, Cao X, Xian M, Fang L, Cai TB, Ji JJ, Tunac JB, Sun D, Wang, P. G.. (2005) "Synthesis and enzyme-specific activation of carbohydrate-geldanamycin conjugates with potent anticancer activity."
J Med Chem 48(2), 645-52.
Luo S, Mi X, Xu H, Wang, P. G., Cheng JP.(2004) "Efficient Baylis-Hillman reactions of cyclic enones in methanol as catalyzed by methoxide anion."
J Org Chem ;69(24), 8413-22.
Cai TB, Lu D, Landerholm M, Wang, P. G.. (2004) "Sialated diazeniumdiolate: a new sialidase-activated nitric oxide donor."
Org Lett 6(23), 4203-5.
Chen M, Liu X, Wang Z, Song J, Qi Q, Wang, P. G.. (2004) "Modification of plant N-glycans processing: the future of producing therapeutic protein by transgenic plants."
Med Res Rev 25(3), 343-60. Review.
Nahalka J, Wu B, Shao J, Gemeiner P, Wang, P. G.. (2004) "Production of cytidine 5'-monophospho-N-acetyl-beta-D-neuraminic acid (CMP-sialic acid) using enzymes or whole cells entrapped in calcium pectate-silica-gel beads."
Biotechnol Appl Biochem 40(Pt 1), 101-6.
Andreana PR, Kowal P, Janczuk AJ, Wang, P. G.. (2004) "Alpha-Galactosyl trisaccharide epitope: Modification of the 6-primary positions and recognition by human anti-alphaGal antibody."
Glycoconj J 20(2), 107-18.
Luo S, Wang, P. G., Cheng JP.(2004) "Remarkable rate acceleration of imidazole-promoted Baylis-Hillman reaction involving cyclic enones in basic water solution."
J Org Chem 69(2), 555-8.
Xian M, Fatima Z, Zhang W, Fang J, Li H, Pei D, Loo J, Stevenson T, Wang, P. G.. (2004) "Identification of alpha-galactosyl epitope mimetics through rapid generation and screening of C-linked glycopeptide library."
J Comb Chem 6(1), 126-34.
Cai TB, Tang X, Nagorski J, Brauschweiger PG, Wang, P. G.. (2003) "Synthesis and cytotoxicity of 5-fluorouracil/diazeniumdiolate conjugates.
Bioorg Med Chem 11(23), 4971-5.
Shao J, Li M, Jia Q, Lu Y, Wang, P. G.. (2003) "Sequence of Escherichia coli O128 antigen biosynthesis cluster and functional identification of an alpha-1,2-fucosyltransferase."
FEBS Lett 553(1-2), 99-103.
Zhang J, Kowal P, Chen X, Wang, P. G.. (2003) "Large-scale synthesis of globotriose derivatives through recombinant E. coli."
Org Biomol Chem 1(17), 3048-53.
Zhang J, Chen X, Shao J, Liu Z, Kowal P, Lu Y, Wang, P. G.. (2003) "Synthesis of galactose-containing oligosaccharides through superbeads and superbug approaches: substrate recognition along different biosynthetic pathways."
Methods Enzymol 362, 106-24. No abstract available.
Shao J, Hayashi T, Wang, P. G.. (2003) "Enhanced production of alpha-galactosyl epitopes by metabolically engineered Pichia pastoris."
Appl Environ Microbiol ;69(9), 5238-42.
Zhang Y, Telyatnikov V, Sathe M, Zeng X, Wang, P. G.. (2003) "Studying the interaction of alpha-gal carbohydrate antigen and proteins by quartz-crystal microbalance."
J Am Chem Soc 125(31), 9292-3. No abstract available.
Zhang J, Wu B, Zhang Y, Kowal P, Wang, P. G.. (2003) "Creatine phosphate--creatine kinase in enzymatic synthesis of glycoconjugates."
Org Lett 5(15), 2583-6.
Shao J, Zhang J, Kowal P, Lu Y, Wang, P. G.. (2003) "Efficient synthesis of globoside and isogloboside tetrasaccharides by using beta(1-->3) N-acetylgalactosaminyltransferase/UDP-N-acetylglucosamine C4 epimerase fusion protein."
Chem Commun (Camb) (12), 1422-3.
Yang J, Fu X, Jia Q, Shen J, Biggins JB, Jiang J, Zhao J, Schmidt JJ, Wang, P. G., Thorson JS.(2003) "Studies on the substrate specificity of Escherichia coli galactokinase."
Org Lett ;5(13), 2223-6.
Jia Q, Cai T, Huang M, Li H, Xian M, Poulos TL, Wang, P. G.. (2003) "Isoform-selective substrates of nitric oxide synthase."
J Med Chem ;46(12), 2271-4.
Tang X, Cai T, Wang, P. G.. (2003) "Synthesis of beta-lactamase activated nitric oxide donors."
Bioorg Med Chem Lett 13(10), 1687-90.
Zhang B, Zhu XQ, Lu JY, He J, Wang, P. G., Cheng JP.(2003) "Polysiloxane-supported NAD(P)H model 1-benzyl-1,4-dihydronicotinamide: synthesis and application in the reduction of activated olefins."
J Org Chem 68(8), 3295-8.
Chen X, Wu B, Wang, P. G.. (2003) "Glucuronides in anti-cancer therapy."
Curr Med Chem Anticancer Agents 3(2), 139-50. Review.
Liu Z, Lu Y, Zhang J, Pardee K, Wang, P. G.. (2003) "P1 Trisaccharide (Galalpha1,4Galbeta1,4GlcNAc) synthesis by enzyme glycosylation reactions using recombinant Escherichia coli."
Appl Environ Microbiol 69(4), 2110-5.
Andreana, P.R., McLellan, J.S., Chen, Y., and Wang,
P.G. (2002) "Synthesis
of 2,6-dideoxysugars via ring-closing olefinic metathesis." Org
Lett.4, 3875-8.
Nahalka, J., Liu, Z., Chen, X., and Wang,
P.G. (2002) "Superbeads:
immobilization in 'Sweet' chemistry." Chemistry 9,
372-7.
Kowal P, and Wang, P.G. (2002) "New UDP-GlcNAc C4 epimerase involved
in the biosynthesis of 2-acetamino-2-deoxy-L-altruronic acid in the
O-antigen repeating units of Plesiomonas shigelloides O17." Biochemistry 41,
15410-4.
Li, H., Shimizu, H., Flinspach, M., Jamal, J., Yang, W., Xian, M.,
Cai, T., Wen, E.Z., Jia, Q., Wang, P.G., and Poulos, T.L. (2002) " The
novel binding mode of N-alkyl-N'-hydroxyguanidine to neuronal nitric
oxide synthase provides mechanistic insights into NO biosynthesis." Biochemistry 41,
13868-75.
Shao, J., Zhang, J., Kowal, P., and Wang,
P.G. (2002) "Donor substrate
regeneration for efficient synthesis of globotetraose and isoglobotetraose." Appl
Environ Microbiol. 68, 5634-40.
Janczuk, A.J., Zhang, W., Andreana, P.R., Warrick, J., and Wang,
P.G. (2002) "The synthesis of deoxy-alpha-Gal epitope derivatives
for the evaluation of an anti-alpha-Gal antibody binding." Carbohydr
Res. 337, 1247-59.
Xian, M., Fujiwara, N., Wen, Z., Cai, T., Kazuma, S., Janczuk, A.J.,
Tang, X., Telyatnikov, V.V., Zhang ,Y., Chen, X., Miyamoto, Y., Taniguchi,
N., and Wang, P.G. (2002) "Novel substrates for nitric oxide synthases." Bioorg
Med Chem. 10, 3049-55.
Akhter, S., Vignini, A., Wen, Z., English, A., Wang,
P.G., and Mutus,
B. (2002) "Evidence for S-nitrosothiol-dependent changes in fibrinogen
that do not involve transnitrosation or thiolation." Proc Natl
Acad Sci U S A. 99, 9172-7.
Shao, J., Zhang, J., Kowal, P., Lu, Y., and Wang,
P.G. (2002) "Overexpression
and biochemical characterization of beta-1,3-N-acetylgalactosaminyltransferase
LgtD from Haemophilus influenzae strain Rd." Biochem
Biophys Res Commun. 295, 1-8.
Chen, Y., Janczuk, A., Chen, X., Wang, J., Ksebati, M., and Wang,
P.G. (2002) "Expeditious syntheses of two carbohydrate-linked cisplatin
analogs." Carbohydr Res. 337, 1043-6.
Zhang, J., Kowal, P., Fang, J., Andreana, P., and Wang,
P.G. (2002) "Efficient
chemoenzymatic synthesis of globotriose and its derivatives with a recombinant
alpha-(1-->4)-galactosyltransferase." Carbohydr Res. 337,
969-76.
Cai, T., Xian, M., and Wang, P.G. (2002) "Electrochemical and
peroxidase oxidation study of N'-hydroxyguanidine derivatives as NO
donors." Bioorg Med Chem Lett. 12, 1507-10.
Andreana, P.R., Xie, W., Cheng, H.N., Qiao, L., Murphy, .DJ., Gu, Q.M.,
and Wang, P.G. (2002) "In situ preparation of beta-D-1-O-hydroxylamino
carbohydrate polymers mediated by galactose oxidase." Org Lett.4,
1863-6.
Wu, B., Zhang, Y., Zheng, R., Guo, C., and Wang,
P.G. (2002) "Bifunctional
phosphomannose isomerase/GDP-D-mannose pyrophosphorylase is the point
of control for GDP-D-mannose biosynthesis in Helicobacter pylori." FEBS
Lett. 519, 87-92.
Wu, X., Tang, X., Xian, M., Brauschweiger, P.G., and Wang,
P.G. (2002) "Synthesis
and cytotoxicities of mannose conjugated S-nitroso-N-acetylpenicillamine
(SNAP)." Bioorg Med Chem. 10, 2303-7.
Wang, P.G., Xian, M., Tang, X., Wu, X., Wen, Z., Cai, T., and Janczuk,
A.J. (2002) "Nitric oxide donors: chemical activities and biological
applications." Chem Rev. 102, 1091-134.
Liu, Z., Zhang, J., Chen, X., and Wang,
P.G. (2002) "Combined
biosynthetic pathway for de novo production of UDP-galactose: catalysis
with multiple enzymes immobilized on agarose beads." Chembiochem. 3,
348-55.
