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Danzhou Yang
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Assistant Professor of Pharmacology and Toxicology; Ph.D.
University of Illinois,
Urbana, 1996 .
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yangd@pharmacy.arizona.edu
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Targeting interactions of anti-cancer drugs and rational drug design
Research Activities
Chemotherapy is an important approach in the treatment of human
cancer. Most of the front line anticancer agents are known to
interact with DNA or DNA topoisomerase enzymes in order to exert
their anticancer effects. In a broad sense, DNA and DNA topoisomerases
can be regarded as the primary targets for numerous antitumor
drugs. A major interest of my research program is to characterize
DNA and protein target interactions of anticancer agents. My research
program involves the implementation of a variety of state-of-the-art
biophysical and biochemical methods, especially high-field NMR
spectroscopy. The variety of complementary methods provides a
powerful approach for obtaining a 3-dimensional view of the target
interactions of anticancer drugs. Understanding structure-function
directed macromolecule-target interactions of anticancer drugs,
and further rational design of improved anticancer agents are
the long-term research goals of our laboratory. Specifically,
we are working on: 1). Interaction of Camptothecin Anticancer
Drugs with DNA and Topoisomerase I. Camptothecin derivatives
display promising antitumor activity over a broad spectrum of
human tumors and are renown for their unique mechanism of action,
inhibition of DNA topoisomerase I. Two water-soluble members of
the camptothecin family, Camptosar (CPT-11) and Hycamtin (topotecan,
TPT), have
recently been approved by the FDA for the treatment of colon cancer
and ovarian cancer, respectively. However, little information
is available concerning drug interactions with topoisomerase I
protein and DNA target sites at the molecular level. Our research
program is to explore the molecular level details of the DNA and
topoisomerase I target interactions of the camptothecin anticancer
drugs. 2). Interaction of Novel Platinum-based Anticancer Drugs
with DNA. 3). Bioinformatics and Cancer-Related Proteins. 4).
Gene and Oligonucleotide-Based Cancer Therapies: Vector Design
and Formulation.
Publications
(Query PubMed for this investigator)
D. Yang, S. Kruszewski, D. P. Curran, D. Bom, H. Josien, S. Zimmer,
and T. G. Burke: The
10-Hydroxy Functionality of the Novel, Highly Lipophilic Silateca
7-t-Butyldimethylsilyl-
10-Hydroxycamptothecin (DB67) and Its 7-[(2-Trimethylsilyl)Ethyl]-Analog
Strongly
Modulates Physicochemical and Pharmacological Properties, Pharmaceutical
Research,
submitted, 2001.
Y. Zhang, F. Yuan, H. Xin, X. Wu, D. K. Rajpal, D. Yang and Z.
Wang: Human DNA
Polymerase ? Synthesizes DNA with Extraordinarily Low Fidelity,
Nucleic Acids Research,
28:4147-4156, 2000
I. Gryczynski, Z. Gryczynski, J. R. Lakowicz, D. Yang, and T. G.
Burke: Fluorescence Spectral
Properties of the Anticancer Drug Topotecan By Steady-State and
Frequency-Domain
Fluorometry with One-Photon and Multi-Photon Excitation, Photochemistry
and Photobiology,
69(4):421-428, 1999.
D. Yang, J. T. Strode, H. P. Spielmann, A. H.-J. Wang and T. G.
Burke: DNA Interactions of
Two Clinical Camptothecin Drugs Stabilize Their Active Lactone Forms,
J. of American
Chemical Society, 120:2979-2980, 1998.
D. Yang and A. H.-J. Wang: The Structural Studies of Interactions
between Anticancer Platinum
Drugs and DNA, Progress in Biophysics and Molecular Biology, 66:81-111,
1996.
D. Yang, S. S. G. E. van Boom, J. Reedijk, J. H. van Boom, N. Farrell
and A. H.-J. Wang: A
novel DNA structure induced by the new dinuclear anticancer compound
m-(1,4-diaminobutane)
-bis[trans-diamminechloroplatinum (II)] crosslinked to a GpC site
in DNA, Nature Structural
Biology, (cover article) 2:577-586, 1995.
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