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Eric C. Long
Japan Society for the Promotion of Science, Invitation
Fellowship, 2004; Indiana University Trustees Teaching Award, 2002,
2001; Purdue School of Science Teaching Award, 1999; Indiana
University Teaching Excellence Recognition Award, 1999, 1997; Purdue
Research Foundation Summer Faculty Fellow, 1992.
Research
Intense interest in the design, synthesis and study
of DNA and RNA binding metal complexes is spurred by their ability
to act as anticancer agents, nucleic acid structural probes, and
models to understand the molecular recognition of these vital biopolymers.
In this area, our laboratory is focused on exploring unique metal
complexes with peptide-based ligands. Significantly, peptide ligands
allow the creation of metallopeptides that contain the same chemical
functional groups, such as guanidinium, amino, and amide moieties,
employed by proteins or antitumor natural products for the selective
recognition of DNA and RNA. In addition, the metal center imparts
structure and redox activity to the peptide which lacks these attributes
alone. These features, coupled to the ease of peptide synthesis
and the ability to alter readily the chirality of select α-carbon
stereocenters, allow metallopeptides to function as useful models
to further our knowledge of protein- and antitumor agent-nucleic
acid recognition principles.
 
In light of the above, we are exploiting peptides of the general
form Xaa-Xaa-His (where Xaa is
an
α-amino acid) in the presence of Ni(II), Cu(II), or Co(III)
to generate novel nucleic acid binding and cleaving metallopeptides.
Our goal is to understand how amino acids within the three-dimensional
constraints imposed by a metal center can be used to selectively
and efficiently target nucleic acids, information central to increasing
our understanding of drug- and protein-nucleic acid recognition
phenomena. Further, insight derived from these studies, such as
particular spatial arrangements of chemical functional groups,
could be used to augment the activity of established DNA-interactive
agents or assist in the development of biosynthetic structures
targeted to nucleic acids.
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Representative Publications
Y.-Y. Fang, B. D. Ray, C. A. Claussen, K. B. Lipkowitz,
and E. C. Long, "Ni(II)•Arg-Gly-His-DNA interactions: Investigation
into the basis for minor groove binding and recognition" Journal
of the American Chemical Society, 126, 5403-5412 (2004)
E. C. Long
and C. A. Claussen, "DNA and RNA
recognition and modification by Gly-Gly-His-derived metallopeptides"
in: DNA and RNA Binders-From Small Molecules to Drugs, Demeunynck,
M., Bailly, C., and Wilson, W. D., Eds., Wiley-VCH, 2003 pp.
88-125.
R. Nagane, Koshigoe, T., Chikira, M., and E. C.
Long, "The DNA-bound orientation of Cu(II)•Xaa-Gly-His
metallopeptides", Journal of Inorganic Biochemistry, 83,
17-23 (2001).
D. C. Ananias and E. C. Long, "Highly selective DNA modification
by ambient dioxygen-activated Co(II)•Lys-Gly-His metallopeptides"
Journal of the American Chemical Society, 122, 10460-10461 (2000).
E.C. Long, “Ni(II)•Xaa-Xaa-His metallopeptide DNA/RNA
interactions”, Accounts of Chemical Research, 32, 827-836
(1999).
X. Huang, M.E. Pieczko, and E.C. Long, “Combinatorial optimization
of the DNA cleaving Ni(II)• Xaa-Xaa-His metallotripeptide
domain”, Biochemistry, 38, 2160–2166 (1999).
I.J. Brittain, X. Huang, and E.C. Long, “Selective recognition
and cleavage of RNA loop structures by Ni(II)•Xaa-Gly-His
metallopeptides”, Biochemistry, 37, 12113-12120 (1998).
Q. Liang, D.C. Ananias, and E.C. Long, “Ni(II)•Xaa-Xaa-His
induced DNA cleavage: deoxyribose modification by a common “activated”
intermediate derived from KHSO5, MMPP, or H2O2”,
Journal of the American Chemical Society, 120, 248-257 (1998).
D.C. Ananias and E.C. Long, “DNA strand scission by dioxygen
+ light-activated Co metallopeptides”, Inorganic Chemistry,
36, 2469-2471 (1997).
Q. Liang, P.D. Eason, and E.C. Long, “Metallopeptide-DNA
interactions: site-selectivity based on amino acid composition
and chirality”, Journal of the American Chemical Society,
17, 9625-9631 (1995).
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