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Professor Linhardt
received his undergraduate degree from Marquette University,
and his MA and PhD in Organic Chemistry from Johns Hopkins University.
He did postdoctoral work in the Chemical Engineering department
at MIT. He joined the Chemistry department at RPI in the Fall
of 2003 as a Constellation professor.
Research in my laboratory focuses on complex carbohydrates. Glycoprotein,
proteoglycans and other glycoconjugates are prepared by fermentation
using recombinant technology, extraction from tissues or chemical
and enzymatic synthesis. After determining the structure of these
molecules, we study their biological activities . By establishing
a structure-activity relationship, these molecules often become
lead compounds for new drug development.
Synthetic Carbohydrate Chemistry
Some carbohydrates are not accessible from natural sources. Our
carbohydrate chemistry group relies on chemical and enzymatic
synthesis to prepare target carbohydrates for biological evaluation.
The current focus of this group is to prepare acidic carbohydrates,
particularly ones that are catabolically stable. Two current targets
include: sTn C-glycoside tumor antigen analogue, for use as a
cancer vaccine; and GM4 C-glycoside, a ganglioside important in
regeneration of damaged nerve fibers. Combinatorial synthesis
of acidic carbohydrates for high through-put activity screening
is being investigated.
Biochemistry and Structural Biochemistry
This project area focuses on the preparation, purification and
characterization of carbohydrates and glycoconjugates. We then
use a variety of separation methods, including affinity reverse
micellar extraction techniques, to purify these glycoconjugates
and determine their structure by both microsequencing techniques
and modern spectroscopic methods.
Biophysical Chemistry
Most carbohydrates exhibit biological activity by modulating
the activity of proteins, such as enzymes and receptors. The
biophysical chemistry subgroup studies the kinetics and thermodynamics
of protein-carbohydrate interaction. We rely primarily on isothermal
titration calorimetry to study interaction thermodynamics and
surface plasmon resonance spectrometry to study interaction
kinetics. Finally, x-ray crystallography and NMR solution structure
is used in conjunction with molecular modeling to examine the
molecular contacts in the protein carbohydrate complex.
Chemoenzymatic Synthesis of Neuraminic Acid Containing C-Glycoside
Polymers, Wang, Q.; Dordick, J. S.; Linhardt, R. J. Organic
Letters, 5, 1187-1189, 2003.
Synthesis of a C -Glycoside Analog of sTn: an HIV
and Tumor Associated Antigen, Kuberan, B.; Sikkandar, S.A.;
Tomiyama, H.; Linhardt, R.J. Angewandte Chemie Int. Ed.,
42, 2073-2075, 2003.
Evaluation of Counter-Ions for Electrospray Ionization Mass
Spectral Analysis of Highly Sulfated Carbohydrates, Gunay, N.S.;
Tadano-Aritomi, K.; Toida, T.; Ishizuka, I.; Linhardt, R.J.
Analytical Chemistry, 75, 3226-3231,
2003.
Perspective: 2003 Claude S. Hudson Award Address in Carbohydrate
Chemistry. Heparin: Structure and Activity, Linhardt, R. J.
Journal of Medicinal Chemistry, 46,
2551-2554, 2003.
Dialkyl imidazolium benzoates - room temperature ionic liquids
useful in the peracetylation and perbenzoylation of simple and
sulfated saccharides, Murugesan, S.; Karst, N.; Islam, T.; Wiencek,
J.M.; Linhardt, R.J. Synlett, 9, 1283-1286,
2003.
Cellular Binding of Hepatitis C Virus Envelope Glycoprotein
E2 Requires Cell Surface Heparan Sulfate, Barth, H.; Schäfer,
C.; Adah, M. I.; Zhang, F.; Linhardt, R. J.; Toyoda, H.; Kinoshita-Toyoda,
A.; Toida, T.; van Kuppevelt, T. H.; Depla, E.; von Weiszäcker,
F.; Blum, H.E.; Baumert, T.F. Journal of Biologic Chemistry,
278, 41003-41012, 2003.
The First Total Synthesis of Calabricoside A, Du, Y.; Wei,
G.; Linhardt, R. J. Tetrahedron Letters, 44,
6887-6890, 2003.
Heparin-Protein Interactions, Capila, I.; Linhardt, R.J. Angewandte
Chemie Int. Ed., 41, 390-412, 2002; Angewandte
Chemie 114, 426-450, 2002.
Inhibition of Apolipoprotein E- Related Neurotoxicity by Glycosaminoglycans
and their Oligosaccharides, Bazin, H. G.; Marques, M. A.; Owens,
A. P.; Linhardt, R.J.; Krutcher, K. A. Biochemistry,
41, 8203-8211, 2002.
Synthesis and Application of Carbohydrate-Containing Polymers,
Wang, Q.; Dordick, J. S.; Linhardt, R. J. Chemistry of Materials,
14, 3232-3244, 2002.
Structural Basis for the Therapeutic Activity of Sucrose Octasulfate
(SOS), Yeh, B. K.; Plotnikov, A. N.; Eliseenkova, A. V.; Green,
D.; Pinnel, J.; Polat, T.; Gritli-Linde, A.; Linhardt, R. J.;
Mohammadi, M.; Molecular and Cellular Biology, 22,
7184-7192, 2002.
Ultra-High Resolution Separation Comes of Age, Linhardt, R.J.;
Toida, T. Science, 298, 1441-1442,
2002.
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