Research

The research interests of my group are focused on the study of low molecular weight DNA and RNA binding agents due to the ability of such compounds to act as anticancer drugs, nucleic acid structural probes, and models to understand the fundamental molecular recognition of these vital biopolymers. We are engaged in two research directions: (1) the development and application of new experimental approaches to accelerate the discovery of DNA and RNA-targeted agents and (2) DNA recognition studies of synthetic, peptide-based agents, as well as a family of naturally-occurring, clinically used anti-tumor glycopeptides – the bleomycins. 

In the first area, we have developed a high-throughput screening (HTS) strategy leading to the rapid identification of novel DNA-targeted compounds from large compound libraries (Glass et al., 2010). In addition, we have applied a microplate-based fluorescent intercalator displacement (FID) assay to determine the site-selectivities of DNA-targeted compounds (Lewis & Long, 2006) and succeeded in coupling the information gained from this assay (knowledge of preferred DNA binding sites) to a host-guest DNA crystallization system leading to full structural analyses of select DNA binders (Goodwin et al. 2006; Long, Georgiadis et al., 2009). This latter aspect of our work is being performed in collaboration with Prof. M. Georgiadis and presently involves extending this work to alternative nucleic acid structures and the characterization of the unique compounds gleaned from screening thus far.

In the second area, we have been investigating the DNA recognition capabilities of synthetic metallopeptides for a number of years (Long, Fang et al. 2009; Fang et al. 2006) and have, more recently, focused our attention (once again) on a naturally-occurring metallopeptide: bleomycin. In the area of bleomycin-DNA recognition, we have applied the FID plate assay described above (Lewis & Long, 2006), as well as the host-guest crystallization system (again, in collaboration with Prof. Georgiadis), leading to a comprehensive determination of the preferred DNA binding sites of bleomycin and the first crystal structure of a DNA-bound metallobleomycin, as shown below (Goodwin et al. 2008; Long, Georgiadis et al, 2009). Following up on this initial work, we are now examining details of the interactions that occur between DNA and a bound bleomycin as well as alternative DNA sites of biological interest.

Education

• B.S., Albright College, 1984
• Ph.D., University of Virginia, 1988
• Fellow of the Jane Coffin Childs Memorial Fund for Medical Research, Columbia University and the California Institute of Technology, 1989-91

Publications & Professional Activity

Editorial

Editor, Bioinorganic Chemistry: Cellular Systems & Synthetic Models, ACS Symposium Series Volume 1012 (co-edited with M. J. Baldwin), 2009

Associate Editor, Current Bioactive Compounds (2008-Present)

Editorial Advisory Board, Current Organic Synthesis (2009-Present)

Editorial Advisory Board, The Open Natural Products Journal (2007-Present)

Select Publications

G. Lin, Y. Jian, K. J. Dria, E. C. Long and Lei Li “Reactivity of Damaged Pyrimidines: DNA Cleavage via Hemiaminal Formation at the C4 Positions of the Saturated Thymine of Spore Photoproduct and Dihydrouridine” Journal of the American Chemical Society 2014, 136, 12938-12946.

M. A. Lewis, K. M. Williams, Y.-Y. Fang, F. A. Schultz and E. C. Long “DNA Cleaving 'Tandem-Array' Metallopeptides Activated With KHSO5: Towards the Development of Multi-Metallated Bioactive Conjugates and Compounds”  Current Bioactive Compounds 2014, 10, 13-20.

M. L. Garner, T. M. Georgiadis, J. B. Li, T. Wang and E. C. Long “Solid-Phase Synthesis of Amidine-Substituted Phenylbenzimidazoles and Incorporation of this DNA Binding  and Recognition Motif into Amino Acid and Peptide Conjugates” Amino Acids 2014, 46, 1297-1303. DOI: 10.1007/s00726-014-1691-5 

M. L. Garner, T. M. Georgiadis, J. B. Li, T. Wang and E. C. Long “Solid-Phase Synthesis of Amidine-Substituted Phenylbenzimidazoles and Incorporation of this DNA Binding  and Recognition Motif into Amino Acid and Peptide Conjugates” Amino Acids 2014, published online 2/24/14, DOI: 10.1007/s00726-014-1691-5 

E. C. Long, H. Fenniri, O. Martin and P. Langer “A tribute to a living legend” Current Bioactive Compounds 2012, 8, i.

D. W. Raches, S. Xiao, P. Kusumanchi, J. Yalowitz, P. Sanghani, E. C. Long, A. C. Antony and H. N. Jayaram “Cloning, Expression, and Characterization of Mouse (Mus Musculus) Nicotinamide 5´-Mononucleotide Adenylyltransferase-2” Medicinal Chemistry 2011, 7, 718-726.

L. S. Glass, A. Bapat, M. R. Kelley, M. M. Georgiadis and E. C. Long “Semi-automated high throughput fluorescent intercalator displacement-based discovery of cytotoxic DNA binding agents from a large compound library” Bioorganic & Medicinal Chemistry Letters 2010, 20, 1685-1688.

A. Bapat, L. S. Glass, M. Luo, M. L. Fishel, E. C. Long, M. M. Georgiadis and M. R. Kelley “Novel small molecule inhibitor of apurinic/apyrimidinic endonuclease 1 blocks proliferation and reduces viability of glioblastoma cells” Journal of Pharmacology & Experimental Therapeutics 2010, 334,988-998.

B. Laing, L. Barrow-Laing, M. Harrington, E. C. Long and D. E. Bergstrom “Properties of double-stranded oligonucleotides modified with lipophilic substituents” Bioconjugate Chemistry 2010, 21, 1537-1544.

Y.-Y. Fang, V. R. Morris, E. C. Long, G. M. Lingani and W. M. Southerland “Genome-targeted drug design: understanding the netropsin-DNA interaction” The Open Conference Proceedings Journal 2010, 1, 157-163.

E. C. Long, M. M. Georgiadis, K. D. Goodwin and M. A. Lewis “New approaches to analyzing the site-selectivities and crystal structures of DNA targeted metal complexes” Chapter 5 in: Bioinorganic Chemistry: Cellular Systems and Synthetic Models, E. C. Long and M. J. Baldwin, Eds., ACS Symposium Series Volume 1012; American Chemical Society: Washington, D. C., 2009, pp 63-80.

E. C. Long, Y.-Y. Fang and M. A. Lewis “DNA minor groove recognition by Ni(II)• and Cu(II)•Gly-Gly-His-derived metallopeptides” Chapter 14 in: Bioinorganic Chemistry: Cellular Systems and Synthetic Models, E. C. Long and M. J. Baldwin, Eds., ACS Symposium Series Volume 1012; American Chemical Society: Washington, D. C., 2009, pp 219-241.

L. S. Glass, B. Nguyen, K. D. Goodwin, C. Dardonville, W. D. Wilson, E. C. Long, and M. M. Georgiadis "Crystal structure of a trypanocidal 4, 4´-bis(imidazolinylamino)diphenylamine bound to DNA" Biochemistry 2009, 48, 5943-5952.

K. D. Goodwin, M. A. Lewis, E. C. Long and M. M. Georgiadis "The crystal structure of DNA-bound Co(III)•bleomycin B2: Insights on intercalation and minor groove binding" Proceedings of the National Academy of Sciences, U.S.A, 2008, 105, 5052-5056.

M. J. Murcia, D. L. Shaw, C. A. Naumann and E. C. Long "Fluorescence correlation spectroscopy of CdSe/ZnS quantum dot bioimaging probes with ultra-thin biocompatible coatings" Optics Communications, 2008, 281, 1771-1780.

Y. Jin, M. A. Lewis, N. H. Gokhale, E. C. Long and J. A. Cowan "Influence of sterochemistry and redox potentials on the single- and double-strand DNA cleavage efficiency of Cu(II)• and Ni(II)•Lys-Gly-His-derived ATCUN metallopeptides" Journal of the American Chemical Society, 2007, 129, 8353-8361.

F. A. Tanious, W. Laine, P. Peixoto, C. Bailly, K. D. Goodwin, M. A. Lewis, E. C. Long, M. M. Georgiadis, R. R. Tidwell and W. D. Wilson "Unusually strong binding to the DNA minor groove by a highly twisted benzimidazole-diphenylether: Induced fit and bound water" Biochemistry, 2007, 46, 6944-6956.

H. Hamada, Y. Abe, R. Nagane, Y.-Y. Fang, M. A. Lewis, E. C. Long and M. Chikira "DNA-fiber EPR investigation of the influence of amino-terminal residue stereochemistry on the DNA binding orientation of Cu(II)•Gly-Gly-His-derived metallopeptides" Journal of Inorganic Biochemistry, 2007, 101, 1529-1536.

K. D. Goodwin, M. A. Lewis, F. A. Tanious, R. R. Tidwell, W. D. Wilson, M. M. Georgiadis and E. C. Long "A high-throughput, high-resolution strategy for the study of site-selective DNA binding agents: Analysis of a 'highly twisted' benzimidazole-diamidine" Journal of the American Chemical Society 2006, 128, 7846-7854.

Y.-Y. Fang, K. B. Lipkowitz and E. C. Long "Molecular dynamics simulations of the orientation of Ni(II)•Gly-Gly-His and Ni(II)•Arg-Gly-His metallopeptide-DNA Association" Journal of Chemical Theory & Computation 2006, 2, 1453-1463.

Y.-Y. Fang, C. A. Claussen, K. B. Lipkowitz and E. C. Long "Diastereoselective DNA cleavage recognition by Ni(II)•Gly-Gly-His-derived metallopeptides" Journal of the American Chemical Society 2006, 128, 3198-3207.

M. A. Lewis and E. C. Long "Fluorescent intercalator displacement analyses of DNA binding by the peptide-derived natural products netropsin, actinomycin, and bleomycin" Bioorganic & Medicinal Chemistry 2006, 14, 3481-3490.

M. J. Murcia, D. L. Shaw, H. Woodruff, C. A. Naumann, B. A. Young and E. C. Long "Facile sonochemical synthesis of highly luminescent ZnS-shelled CdSe quantum dots" Chemistry of Materials 2006, 18, 2219-2225.

K. D. Goodwin E. C. Long, E. C. and M. M. Georgiadis "A host-guest approach for determining drug-DNA interactions: An example using netropsin" Nucleic Acids Research 2005, 33, 4106-4116.

Affiliations

• Member, The American Chemical Society
• Chemical Synthesis and Organic Drug Lead Development

Awards

• 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