Professor of Chemistry, Brooklyn College of the City University of New York
Sc. (Hons) Biochemistry, The University of Salford, UK
Our laboratory is focused on biophysical studies of the shape, dynamics and interactions of complex biomolecules, and how these factors influence important biological functions. Our current interest focuses on an unusual DNA structure, which has been shown to have important significance for cancer research studies. So-called “G-quadruplex forming” base-sequences found in DNA, either at the end of chromosomes (telomeres) or within the genomic-DNA, can fold under certain cellular conditions into a four-stranded “knot-like” structure. These “knots” are reported to play an important role in controlling the activity of various cancer causing oncogenes. Additionally, G-quadruplex-“knots” inhibit the activity of the enzyme telomerase, reported to be over-expressed in over 90% of the solid-state tumors analyzed, resulting in cell immortality and possible tumorigenesis. We are using sophisticated optical spectroscopic methods, including fluorescence spectroscopy and circular dichroism measurements, to examine how the folding and unfolding of DNA G-quadruplex structures can be modulated by the binding of small molecules that are potentially useful as anti-cancer drugs. Promotion of DNA strand folding into G-quadruplex structures can serve as a strategy for inhibiting the telomerase enzyme and tumor formation. In particular, we are exploring the ability of various porphyrin and fluorenone-derivatives to bind selectively to G-quadruplex-forming sequences and promote DNA folding. In addition we are exploring the altered spectroscopic characteristics arising from selective binding of these small molecules to the folded state, to develop a rapid and sensitive drug screening method.
Desamero, J., and Davenport, L. (2020) ‘Mapping Lateral Loop Conformational Switching of the Telomeric DNA G-Quadruplex on NMM Porphyrin Binding Using Fluorescent Guanine Analogs.’ Biophysical Journal, in press (ABSTRACT).
Kopkalli, Y., Celius, T.C., Dickson-Karn, N.M., Davenport, L., Williams, B.W. (2019) ‘The Solvatochromic Response of Benzo[a]fluorenone in Aprotic Solvents Compared with Benzo[b]fluorenone and 9-Fluorenone.’ J. Physical Organic Chemistry. Early publication (e3994) (https://doi.org/10.1002/poc.3994).
Mahendran, A., Kopkalli, Y., Ghosh, G., Ghogare, A., Minnis, M., Kruft, B.I., Aebisher, D., Davenport, L., Greer, A. (2011) ‘A Hand-held Fiber-Optic Implement for the Site-specific Delivery of Photosensitizer and Singlet Oxygen.’ Photochemistry and Photobiology, 87, 1330-1337. (http://dx.doi.org/10.1111/j.1751-1097.2011.00971.x).
Martinez, A., Rajapakse, Ch. S. K., Naoulou, B., Kopkalli, Y., Davenport, L. and Sanchez-Delgado, R.A. (2008) ‘The Mechanism of Antimalarial Action of the Ruthenium(II)-Chloroquine Complex [RuCl2(CQ)]2.’ Journal of Biological Inorganic Chemistry 13, 703-712. (http://dx.doi.org/10.1007/s00775-008-0356-9).
Jamison, J.L., Davenport, L., and Williams, B.W. (2006) ‘Solvatochromism in the Aromatic Ketone Benzo(b)Fluorenone.’, Chem. Phys. Letts., 422, 30-35. (http://dx.doi.org/10.1016/j.cplett.2006.02.014).
Davenport, L. ‘G-Quadruplex Binding Assays and Compounds Therefor.’ (2017) US Patent No. 9,598,719.
Davenport, L. ‘G-Quadruplex Binding Assays and Compounds Therefor.’ (2010) US Patent No. 7,781,163.
Davenport, L., and Targowski, P., ‘A Direct Method for the Correction of Pressure Induced Scrambling of Polarized Fluorescence Intensities.’ (2006) US Patent No. 7,126,683.
Davenport, L., and Targowski, P., ‘A Direct Method for the Correction of Pressure Induced Scrambling of Polarized Fluorescence Intensities.’ (2005) US Patent No. 6,956,646.
Davenport,, ‘Fluorescent Phospholipid Analogs and Fatty Acid Derivatives’, (1994) US Patent No. 5,322,794.
Grants over the last 5 years