The Harry C. Allen Jr. Symposium Series on Bonding and
Structure was established in 1986 in recognition of Dr.
Allen's many years of service to Clark University. Now
Professor Emeritus, Allen joined Clark in 1969 as Chair of
the Department of Chemistry. Later administrative roles
included Dean of the Graduate School, Associate Provost,
and Dean of Research.
Allen was a native of Saugus, Massachusetts and alumnus
of Northeastern University (B.S.), Brown University
(Sc.M.), and the University of Washington (Ph.D.). After
Postdoctoral work at Harvard and Cambridge Universities,
and a year of teaching at Michigan State University, Allen
joined the National Bureau of Standards as a researcher in
molecular structure and spectroscopy. In 1961 he became
Chief of the Analytical Inorganic Division, and, in 1965,
Deputy Director of the Institute for Materials. From 19661969 he served as Assistant Director of the Bureau of
Mines.
Author of more than 60 published works and past associate
editor of the Journal of Chemical Physics, Allen also
received awards for outstanding service from the United
States Department of Commerce, National Bureau of
Standards, and the Bureau of Mines.
CLARK
UNIVERSITY
Gustaf H. Carlson
School of Chemistry and Biochemistry
950 Main Street
Worcester, MA 01610-1477
(508) 793-7116

Twenty-Fifth Annual
HARRY C. ALLEN JR.
SYMPOSIUM

April 5, 2014
1:00 p.m.
Sackler Sciences Center
Room S120
ABSTRACTS OF PRESENTED TALKS
Paul Wender
Department of Chemistry
Stanford University
Computer-Guided, Synthesis-Informed Design Directed at
Transformative Therapies for AIDS, Alzheimer’s and Cancer
Research in our group is directed at addressing problems in chemistry, biology,
medicine and materials science. A special emphasis is placed on addressing
unsolved problems such as the eradication of HIV/AIDS, treatment of cognitive
dysfunction through synaptogenesis, and treatment of cancer using non-toxic
small molecule immunotherapy. These and related projects rely heavily on the
synthesis-informed, computer-guided design of molecules with unusual if not
unique biological functions (Function-Oriented Synthesis) and the development of
new reactions and strategies for their step economical synthesis. This lecture will
cover the background, progress and prospects of projects directed at the titled
therapeutic indications. Pertinent recent studies from our group can be found
in Proc. Natl. Acad. Sci. USA 2013, 11698; Accts, 2013, ASAP; Nature
Chemistry 2012, 705; Oncotarget 2012, 58; J. Am. Chem. Soc. 2011, 9228; Proc.
Natl. Acad. Sci. USA 2011, 6721; Clinical & Experimental Immunology 2009, 158,
186; Nature 2009, 197; Neurobiology of Disease 2009, 332; Science 2008, 649.
The Intersection of
Organic Chemistry, Biology and Medicine
1:00 pm ...........................................................................Amy Anderson
2:00 pm ............................................................... Eranthie Weerapana
3:00 pm ............................................... Coffee Break/Poster Session
4:00 pm ...............................................................................Paul Wender
5:00 pm ........................................ Theoharides and Poster Awards
Amy Anderson
Eranthie Weerapana
Department of Pharmaceutical Sciences
University of Connecticut
Department of Chemistry
Boston College
Structure-Based Design of New Antibiotics to Overcome
Drug Resistance
Chemical Proteomic Strategies to Investigate
Reactive Cysteines
Antibiotic resistance is a significant healthcare challenge that limits the useful
lifetime of our best drugs and necessitates the active development of nextgeneration antibiotics to ensure continued success in the fight against infectious
disease. These next-generation antibiotics not only need to be active against
current resistant strains but also must be less prone to the development of new
resistance, requiring both a retrospective and prospective consideration of
resistance in drug development. One of the most prevalent mechanisms of drug
resistance involves mutation of the target that reduces drug affinity while
maintaining native function. Understanding the structural basis of these
resistance-conferring mutations enables the design of compounds that overcome
these hurdles. We have used a structure-based approach to develop a series of
antifolate compounds that target dihydrofolate reductase (DHFR) from drugresistant Staphylococcus aureus. These compounds are not only effective against
current isolates of methicillin-resistant S. aureus (MRSA) infection but also display
a low propensity toward the generation of new resistance-conferring mutations.
Cysteine residues play diverse functional roles in proteins including catalysis,
metal-binding, structural stabilization and redox regulation. Our lab applies
chemical probes and quantitative mass-spectrometry methods to identify
functional cysteines in the human proteome. Our studies have generated covalent
activity-based probes for diverse enzyme families, and have revealed novel modes
of protein regulation through cysteine residues.