Control of Gene Expression to Anticancer Drug Design and Development
Photograph
Moses Lee
Synthetic Methodology
Dean of Natural Sciences
and Professor of Chemistry
Me
N
Me
Cl
R1
CO2Et
X
Y
NR
2
O
O
Z
O
O
OBn
R3
Tel: (616) 395-7190
Email: lee@hope.edu
B.S., University of Guelph, Canada, 1983
Ph.D., University of Guelph, 1986
N Me
Me
Medicinal Chemistry - Anticancer Drugs
N
Spirogen Ltd. U.K., “Polyamide-PBD derivatives”
Arnold Beckman Foundation, “Beckman Scholar”
OH
NH
H3C
O
OH
N
O
N
H
N
H
OCH3
OCH3
OCH3
H3CO
CC-1065
O
• Apoptosis induction
DNA interactive
• Anti-angiogenesis
- Solid tumor
- Low toxicity
- Drug targeting
(ADEPT; ETPT)
NH2
O
N
Organic Chemistry, Synthesis, Biochemistry,
and Medicinal Chemistry
2007 Group
OCH3
OPO3= H3CO
Combretastatin A4 phosphate
DNA Sequence Specific Recognition
Medicine
NSF, “Tuning the Thermodynamic and Kinetic Properties of the
Diagnostics
Binding of Hairpin Polyamides to Their Cognate DNA Sequences,
Engineering
-genetic disposition
-abnormal DNA
Molecule-DNA Complex
• Homeland security
• Sequence specificity
• Structure and conformation
• Molecular dynamics
through Incorporation of Intercalating and Threading Agents”
GSK, "Design and Synthesis of Novel H-Pin Polyamides"
• Biosensors
K.L. Buchmueller, S.L. Bailey,* D.A. Matthews,* Z.T. Taherbhai,* T.
Brown, J. Register,* Z.S. Davis,* C.D. Bruce, B. Nguyen, W.D.
Wilson, C. O’Hare, J.A. Hartley, and M. Lee, 2006, Physical and
Structural Basis for the Strong Interactions of the –ImPy– Central
Pairing Motif in the Polyamide, f-Im-Py-Im. Biochemistry 45, 1355113565.
B. Purnell*, A. Sato, A. O’Kelley,* C. Price,* K. Summerville,* S.
Hudson, C. O’Hare, K. Kiakos, J. A. Hartley, T. Asao and M. Lee,
2006, DNA Interstrand Crosslinking Agents: Synthesis, DNA
Interactions, and Cytotoxicity of Dimeric Achiral seco-amino-CBI and
Conjugates of Achiral seco-Amino-CBI with Pyrrolobenzodiazepine
(PBD). Bioorg. Med. Chem. Lett. 16, 5677-5681. (*Undergraduates)
Molecular biology, biochemistry,
H3C
CH3
N
H
N
O N
H3C
H
N
H
N
O N
H3C
R
N O
CH3
O N
H3C
R = NO2
H2, 5% Pd-C, MeOH
R = NH2
N
N O
CH3
H
N
N
synthesis
H
N
H
N
CO2H
N O
CH3
PyBOP, DIPEA
CH2Cl2, r.t.
(37% from R = NO2)
• Gene control
• Anticancer drugs
-resistance
biophysical, computational chemistry
Design,
H
N
Cell &
animal
biology
N O
CH3
H3C
CH3
N
H
N
O N
H3C
H
N
N
H
N
N O
CH3
H
N
O N
H3C
JH-37
N
H
N
N O
CH3
H
N
O N
H3C
O
+