FIRST SINGAPORE MINI-SYMPOSIUM ON MEDICINAL CHEMISTRY: ADVANCES IN
SYNTHESIS AND SCREENING
Time: July 6, 2005
Venue: LT31, Faculty of Science, NUS
Organized by
Faculty of Science and Office of Life Sciences, NUS
Chair: Prof Mei Lin Go, Program Leader of the Medicinal Chemistry Program, NUS
The Medicinal Chemistry Program established under the Experimental Therapeutics
Platform of the Office of Sciences is a multidisciplinary initiative involving departments
in the Faculties of Science (Chemistry, Pharmacy, Biological Sciences), Medicine
(Pharmacology) and Engineering (Chemical and Environmental Engineering). The
program aims to establish Singapore as a world renowned centre for medicinal chemistry
research and to promote collaborative research between academia, research institutes and
pharmaceutical companies. In addition, the program is committed to manpower training
in the area of medicinal chemistry.
On July 6, 2005, the medicinal chemistry program is organizing a one-day mini
symposium entitled “First Singapore mini-symposium on medicinal chemistry: advances
in synthesis and screening”. There will be four international speakers, together with two
local speakers, who are confirmed to deliver lectures in this symposium. Details of the
speakers are listed below:
1.
2.
3.
4.
5.
6.
Professor Hisakazu MIHARA, Tokyo Institute of Technology, Japan
Professor Yoshinobu Baba, Nagoya University, Japan
Professor Injae Shin, Yonsei University, Korea
Professor Itaru Hamachi, Kyushu University, Japan
Professor Yulin Lam, National University of Singapore, Singapore
Professor Martin J. Lear, National University of Singapore, Singapore
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Tentative Schedule (updated on Jun 4, 2005)
July 6, 2005
Time
9:00 – 9:05am
9:05 – 9:50am
9:50 – 10:35am
10:35 – 11:05am
11:05 – 11:50am
11:50am – 2:30pm
2:30 – 3:15pm
3:15 – 4:00pm
4:00 – 4:45pm
4:45pm
Speaker
Title
Opening Remarks
Professor Hardy Chan
Vice Dean for research,
FOS/NUS
Designed Peptide Microarrays for
Professor Hisakazu Mihara
Tokyo Institute of Technology Protein Detection and
Japan
Characterization
Chemical Approaches to Study
Professor Injae Shin
Yonsei University
Biological Processes: Chemical
Korea
Genomics and Chemical Glycomics
Coffee break
Professor
Yulin
Lam Sulfones in Combinatorial Synthesis
National
University
of
Singapore, Singapore
Lunch
Design of Chemo- and Bio-sensors
Professor Itaru Hamachi
Kyoto University
for Substances of Biological
Japan
Importance
Professor Yoshinobu Baba Nanobiodevice for Biomedical and
Nagoya University
Clinical Applications
Japan
Solidifying the Mechanism of Natural
Professor Martin J. Lear
National University of
Enediynes through Synthesis, Design
Singapore, Singapore
and Biological Evaluation
Concluding Remarks
Professor Mei Lin Go
MedChem program leader,
NUS
MC: Prof YiXin Lu
For further information, please contact
Assist. Prof. Shao Q. Yao (chmyaosq@nus.edu.sg) or
Assist Prof Yixin Lu (chmlyx@nus.edu.sg)
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DESIGNED PEPTIDE MICROARRAYS FOR PROTEIN DETECTION AND
CHARACTERIZATION
Hisakazu Mihara
Graduate School of Bioscience and Biotechnology and the COE21 program
Tokyo Institute of Technology, Yokohama 226-8501, Japan
e-mail: hmihara@bio.titech.ac.jp
As advances in genome-wide sciences, the protein-detection microarrays have
been promising technologies providing high-throughput detection for proteins of interest.
To realize such a practical protein-detection system, we have constructed structure-based
microarrays using designed peptides with various secondary structures. Additionally,
peptide libraries with functional groups including phosphorylated or glycosylated amino
acids were established to increase the diversity of such an array system and to apply to
the focused proteomics. Using these libraries, various proteins were characterized to give
their own ‘protein fingerprints’, which correlated with the recognition properties of the
proteins. Furthermore, to develop an easy and high-throughput detection system, various
micro protein-detection methods including a dry peptide array method were
demonstrated. Throughout these studies, it has been demonstrated that the peptide
microarray is one of useful approaches for protein-chip technology. With further
improvement of micro/nano-detection systems, a practical protein-chip technology will
be accomplished.
Chem. Biol., 10, 53-60, 2003; Mol. Divers., 8, 209, 2004; Biopolymers, 76, 129, 2004.
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Chemical Approaches to Study Biological Processes: Chemical genomics and
Chemical glycomics
Professor Injae Shin, Yonsei University, Korea
In the post-genomic era, functional studies of proteins and carbohydrates are main
issues to understand biological phenomena and to exploit more effective therapeutic
agents. To evaluate the biological functions of proteins, we have developed proteinbinding assays using chemical microarrays and cell-based assays to dissect differentiation
mechanism of mammalian cells and zebrafish embryo. On the other hand, we have
developed carbohydrate microarrays to study carbohydrate-protein interactions for
glycomic research in a high-throughput method. In addition, carbohydrate probes that
contain a multivalent carbohydrate ligand, a reporter and a photolabile linker have been
also developed and applied to detecting their binding proteins in cells. In this
presentation, I discuss the preliminary results for these studies.
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SULPHONES IN COMBINATORIAL SYNTHESIS
Yulin Lam
Department of Chemistry, National University of Singapore, 3 Science Drive 3,
Singapore 117543. Email: chmlamyl@nus.edu.sg
An important aspect in solid-phase organic synthesis (SPOS) is the development
of new linker strategies which could efficiently release the target molecule from the resin
and the detached target molecule would have no memory of the immobilization (traceless
cleavage). In this regard, one of our interests is to develop the sulfone linker via polymerbound sodium benzenesulfinate as a traceless linker and explore new applications for it in
SPOS.
Sodium benzenesulfinate is used widely in the preparation of sulfones which play
an important role in organic synthesis. However the use of polymer-bound sodium
benzenesulfinate resin in solid phase synthesis has received little attention. We therefore
decided to examine to possibility of using this resin for a greater variety of synthesis. In
this presentation, traceless synthesis of heterocyclic compounds like will be described.
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Design of Chemo- and Bio-sensors for Substances of Biological Importance
Professor Itaru HAMACHI, Kyoto University, Japan
My group is now developing artificical chemosensors for phosphorylated peptides
and proteins on the basis of interactions between zinc cations and phosphate anions
which can fluorescently sense phosphorylated peptides and proteins in aqueous solution
and SDS PAGE. In other project, lectin, a sugar binding protein, has been successfully
converted to a fluorescent biosensor for saccharides using post-photoaffinity labeling
modification method. The basic strategy and the potential application will be discussed
in my talk in NUS.
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NANOBIODEVICE FOR BIOMEDICAL AND CLINICAL APPLICATIONS
Yoshinobu Baba
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University,
Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan and Health Technology Research Center,
National Institute of Advanced Industrial Science and Technology, Takamatsu 761-0395,
Japan
This presentation will describe the recent development of nano-biodevice
technologies based on the nanofabrication and molecular nanotechnology. The
technologies allow us to develop novel methods for genomics, proteomics, and
glycoproteomics. The methods we have taken appear suitable for biomedical and clinical
applications, including SNPs analysis, mutation analysis, haplotyping, DNA diagnosis,
protein expression analysis, immunoassay, protein disease marker detection, point-ofcare analysis. The methods are also applicable to molecular imaging of cancer cell and
possible photodynamic therapy of cancer.
Nature Biotech., 2004, 22, 337-40; Nature Biotech., 2004, 22, 1360-1; Nano Letters,
2004, 4, 1567-73; Anal. Chem., 2004, 76, 15-22; Anal. Chem., 2004, 76, 3689-93; J.
Proteome Res., 2004, 3, 871-7; Gene Therapy, 2004, 11, 636-44; Lab on a Chip, 2005, 5,
199-204; Anal. Chem.,2005, 77, 2140-2146; Lab on a Chip.,2005, 5, 472-478; Chem.
Comm., 2005, 1980-1982; Genomics, 2005, in press; J. Am. Chem. Soc., 2005, in press.
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Solidifying the Mechanism of Natural Enediynes through Synthesis, Design and
Biological Evaluation
Professor Martin J. Lear, National University of Singapore, Singapore
Highly optimized and reliable approaches to the bicyclic reactive cores of natural
nine-membered enediynes in fully-functionalized form will be discussed. On one hand,
the synthesis and thiol-triggered activation and DNA-cleavage profiles of a stereo-library
of N1999-A2 and its stereoisomers will be discussed, demonstrating that the C11naphthoate is the principal controlling element, both chemically and biologically. On the
other hand, the synthesis of a series of isotopomers of enediyne models, specifically
designed to bear 13C-labels at the supposed radical-forming 3- and 6-positions, will be
given. Solid evidence for the spontaneous Masamune-Bergman cyclization will be
presented, which for the first time demonstrates the differential reactivity of the C3 and
C6 radical positions.
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