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ACS Chem. Biol.,
3 (7),
386–387
10.1021/cb800155p
Web Release Date: July 18, 2008
Copyright © 2008 American Chemical Society
Image courtesy of Yi Li. |
Current position: University of Colorado, Department
of Chemistry and Biochemistry, Ph.D. Student with Prof. Hang (Hubert)
Yin
Education: Moravian College, B.S. in biochemistry,
2007
Nonscientific interests: Running, baking, reading
science fiction
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Protein transmembrane domains are emerging as targets for clinical
therapeutics and diagnostic tools. Chemical biologists have studied
transmembrane domains in a variety of biological systems, and the
fruits of their labors are beginning to surface in the form of rational
and high-throughput design methods. Peptides which recognize protein
transmembrane domains have allowed scientists to deliberately disassemble
and study oligomeric receptors such as T-cell and growth factor receptors.
Novel technologies that lead to specific transmembrane peptide probes
have been reviewed in this article. (Read
Slivka’s
article on p 402.) |
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CLC chloride-transport proteins play many critical physiological
roles, yet our understanding of these proteins has been limited by
a lack of high-affinity inhibitors. This work describes the discovery
of novel inhibitors derived from DIDS, a common low-affinity inhibitor
of many anion-transport proteins. We found that the hydrolysis of
DIDS results in polythiourea products that inhibit three different
CLC proteins more effectively than DIDS itself. These new inhibitors
are the most potent CLC inhibitors yet known and will serve as probes
for dissecting the molecular mechanisms of chloride transport and
as lead compounds for treating disease. (Read
Matulef’s article on p 419 and
Point of View on p 399.) |
Current position: Stanford University, Department
of Molecular and Cellular Physiology, Postdoctoral Fellow with Prof.
Merritt Maduke
Education: Brandeis University, B.A./M.S. in biochemistry,
with Prof. Andrew Szent-Gyorgyi, 1996; University of Washington, Ph.D.
in molecular and cellular biology with Dr. William N. Zagotta, 2002
Nonscientific interests: Hiking, biking, traveling
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Image courtesy of Chris McLain. |
Image courtesy of Yanqiu Yuan. |
Current position: Harvard University, Department of
Chemistry and Chemical Biology, Ph.D. student with Prof. Suzanne Walker
Education: University of Science and Technology of
China, B.S. in chemistry, 2003; Harvard University, Ph.D. in chemistry
and chemical biology, 2008
Nonscientific interests: Reading, traveling, daydreaming
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Resistance to existing antibiotics and a dearth of novel antibiotics
has become a serious threat to public health. My research interest
has been focused on understanding a potential antibiotic target, the
peptidoglycan glycosyltransferases (PGTs) involved in bacterial cell
wall biosynthesis, using biochemical and structural approaches. I
am also studying the inhibition of the PGTs by a natural product moenomycin
A. A co-complex structure of an analog of moenomycin A bound to a
PGT reveals that a network of polar contacts anchoring the inhibitor
in the active site of the enzyme involves residues that are conserved
among PGTs. I also show that an analog that has potential to satisfy
these contacts is biologically active. Thus, the work provides structural
insight into moenomycin inhibition and may direct the design of novel
antibiotics targeted at PGTs. (Read
Yuan’s
article on p 429.) |
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For my Ph.D. work, I achieved formal total synthesis of Taxol,
a highly complex anticancer drug, by utilizing an automated synthesizer
in the Takahashi lab. I was beginning to be interested in how bioactive
small molecules interact with target proteins. After moving to the
Kahne lab, I became involved in the moenomycin project. Moenomycin
is a highly potent natural product antibiotic. In this work, I prepared
chemically modified moenomycin analogs to examine protein–ligand
contacts in detail. We hope our study will facilitate the design of
new antibiotics that target peptidoglycan glycosyltransferases. (Read
Fuse’s article on p 429.) |
Current position: Tokyo Institute of Technology, Department
of Applied Chemistry, Graduate School of Science and Engineering,
Assistant Professor
Education: Tokyo Institute of Technology, B.S. in
chemical engineering, 2000; Tokyo Institute of Technology, Ph.D. in
applied chemistry with Prof. Takashi Takahashi, 2005; Harvard University,
Department of Chemistry and Chemical Biology, Postdoctoral Researcher
with Prof. Daniel E. Kahne, 2006–2008
Nonscientific interests: Casual strolling, socializing
with friends, cooking
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Image courtesy of Shinichiro Fuse. |
Image courtesy of Meng Lv. |
Current position: University of Illinois at Urbana–Champaign,
Micro and Nanotechnology Laboratory, Nano Sensors Group, Ph.D. candidate
with Prof. Brian T. Cunningham
Education: University of Illinois at Urbana–Champaign,
B.A. in electrical engineering and bioengineering, 2004; University
of Illinois at Urbana–Champaign, M.A in electrical engineering,
2006
Nonscientific interests: Musical performance and composition,
ballroom and night club dance, web site development, languages, basketball
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Photonic crystal biosensors have recently been developed by incorporating
photonic crystal structures into standardized microplates. The sensors
have shown high sensitivity in detection of protein–protein,
DNA–protein, protein–small molecule, and cellular interactions.
Through the use of the biosensors, we were able to detect interactions
between apoptosis inducing factor (AIF) and DNA and also detect the
disruption of their interaction by introducing a known inhibitor,
aurintricarboxylic acid. In this paper, we have developed a high-throughput
screening method that was able to quickly and efficiently search for
potential inhibitors for DNA–AIF interaction, which will be
applied to a library of 200,000 compounds. (Read
Chan’s article on p 437.) |
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My research is focused on identifying inhibitors of apoptosis inducing
factor (AIF). AIF is a cytotoxic DNA-binding protein involved in caspase-dependent
and -independent modes of cell death. AIF has been shown to be a relevant
death effector in models of Parkinson’s disease and stroke/ischemia.
In progressing toward inhibitors of AIF, I entered into a collaboration
with the lab of Prof. Brian T. Cunningham at Illinois, where we use
photonic crystal biosensors to detect AIF–DNA binding or a
lack thereof. In the future, we hope to apply this technology to the
disruption of protein–protein and protein–RNA interactions.
(Read
Heeres's article on p 437.) |
Current position: University of Illinois at Urbana–Champaign,
Department of Biochemistry, Ph.D. candidate with Prof. Paul Hergenrother
Education: University of Maryland, B.S. in biochemistry,
2004
Nonscientific interests: Music, guitar, poker
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Image courtesy of Nora Wang. |
See Review by Slivka et al.
See Article by Matulef et al.
See Point of
View by Wulff
See Article by Yuan et al.
See Article by Fuse et al.
See Article by Chan et al.
See Article by Heeres et al.
See In this Issue
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