ROBERT W. ARMSTRONG
Associate Professor; BS, University of California, San Diego; PhD, Colorado State University; NIH Postdoctoral Fellow, Harvard University; Presidential Young Investigator Award.
RESEARCH DESCRIPTION
Our research program in synthetic chemistry relies heavily on synthesis to
solve biologically important problems. This involves the study of
inactivation processes and site-specific recognition of macromolecules
(DNA, RNA, proteins). The program provides an opportunity to combine
synthetic skills with biological evaluation and molecular modeling in order
to understand the mechanism of action of target molecules. In addition, we
are involved in developing new methods of asymmetric synthesis, specifically
the use of DNA as a selective template for asymmetric induction.
We have targeted the synthesis of novel antitumor antibiotics in order
to establish the molecular basis of their specificity. Carzinophilin
and ficellomycin are two such agents whose potential therapeutic capacity
appears to be a result of interference with DNA synthesis. The site
of interaction and the chemical outcome of proposed DNA-drug complexes
are addressed using 2D NOESY and COSY NMR, DNA-footprinting, and isolation
and structure elucidation of chemical fragments. Modeling of new drugs based
on structure activity information and site-selective delivery is also a
primary target of our research. Carbohydrates play a central role as both
a chiral pool for asymmetric chemistry and as templates for biopolymer
synthesis. Thus, unique sugar-based probes are being utilized to
study biopolymer interactions involving large distances (50-100Å)
between interaction sites.
KEY WORDS
Organic and Bioorganic Chemistry: synthesis, structure elucidation,
and mechanism of action of antitumor antibiotics; synthesis and properties
of DNA-and RNA-binding protein mimics; conformational analysis of modified
duplexes (drug-DNA complexes) using 2D NMR techniques; molecular-level
interactions of DNA-binding substrates, DNA-foot printing; synthesis of
modified peptides and DNA; synthesis of C-carbohydrates; glycopeptides.
[ Department *
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Organic Research Interests
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Last
Revision: 10/25/95 // mk
