研究领域

Bio-Organic and Medicinal Chemistry

The long term interest of our lab lies in the understanding,Chemistry Photo Arya Profile design, and discovery of new motifs for the molecular recognition of biological macromolecules. An example of current focus of the laboratory is to understand the features that differentiate B-form from A-form DNA and use this knowledge to discover and design molecules that can specifically recognize A-and B-form DNA. Results obtained are expected to lead to a new pharmacophore for major grooves of A and B-form-DNA recognition that can be further developed to obtain DNA specific molecules with higher affinities and specificities. Minor groove recognition of DNA was driven by the structures of polyamide-DNA complexes solved during the 80s. We expect that a similar characterization of a major groove specific ligand will complete an important missing link in the goal of major groove DNA recognition by small molecules leading to the development of more sequence-specific and higher affinity molecules. Similar tools are being applied to the recognition of higher order DNA and RNA structures, such as triplexes and quadruplexes. The laboratory is equipped to conduct synthesis, physical and structural studies of natural and designed conjugates that are capable of binding to nucleic acids and proteins. These studies are important to both fundamental understanding of macromolecule recognition and to drug development. Based on the information gained from fundamental studies of molecular recognition and supramolecular chemistry, new drug analogues can be synthesized to exhibit altered binding properties with desired biological effects. Ongoing projects combine areas of synthetic organic chemistry, physical organic chemistry, biochemistry, pharmacology, and molecular and cell biology. The interdisciplinary nature of these projects allows students to develop a strong basis for future research. The lab maintains active collaborations with biophysicists, oncologists and infectious disease experts.

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S. Kumar, P. Kellish, W.E. Robinson Jr, D. Wang, D.H. Appella, D.P. Arya, Click Dimers To Target HIV TAR RNA Conformation, Biochemistry.51 (2012) 2331-2347 P.L. Hamilton, D.P. Arya, Natural product DNA major groove binders, Nat. Prod. Rep. 29 (2012) 134-143 H. Xi, E. Davis, N. Ranjan, L. Xue, D. Hyde-Volpe, D.P. Arya, Thermodynamics of nucleic Acid "shape readout" by an aminosugar, Biochemistry. 50 (2011) 9088-9113 S. Kumar, D.P. Arya, Recognition of HIV TAR RNA by triazole linked neomycin dimers, Bioorg. Med. Chem. Lett. 21 (2011) 4788-4792 L. Xue, N. Ranjan, D.P. Arya, Synthesis and spectroscopic studies of the aminoglycoside (Neomycin)-perylene conjugate binding to human telomeric DNA, Biochemistry. 50 (2011) 2838-2849 D.P. Arya, New Approaches Toward Recognition of Nucleic Acid Triple Helices, Acc. Chem. Res. 44 (2011) 134-146 S. Kumar, L. Xue, D.P. Arya, Neomycin-Neomycin Dimer: An All-Carbohydrate Scaffold with High Affinity for AT-Rich DNA Duplexes, J. Am. Chem. Soc. 133 (2011) 7361-7375 N. Ranjan, K.F. Andreasen, S. Kumar, D. Hyde-Volpe, D.P. Arya, Aminoglycoside Binding to Oxytricha nova Telomeric DNA, Biochemistry. 49 (2010) 9891-9903 L. Xue, H. Xi, S. Kumar, et al., Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates, Biochemistry. 49 (2010) 5540-5552 H. Xi, S. Kumar, L. Dosen-Micovic, D.P. Arya, Calorimetric and spectroscopic studies of aminoglycoside binding to AT-rich DNA triple helices, Biochimie. 92 (2010) 514-529 B. Willis, D.P. Arya, Triple recognition of B-DNA by a neomycin-Hoechst 33258-pyrene conjugate, Biochemistry. 49 (2010) 452-469 B. Willis, D.P. Arya, Triple Recognition of B-DNA, Bioorg. Med. Chem. Lett. 19 (2009) 4974-4979 H. Xi, D. Gray, S. Kumar, D.P. Arya, Molecular recognition of single-stranded RNA: neomycin binding to poly(A), FEBS Lett. 583 (2009) 2269-2275 N.N. Shaw, H. Xi, D.P. Arya, Molecular recognition of a DNA:RNA hybrid: sub-nanomolar binding by a neomycin-methidium conjugate, Bioorg. Med. Chem. Lett. 18 (2008) 4142-4145 N.N. Shaw, D.P. Arya, Recognition of the unique structure of DNA:RNA hybrids, Biochimie. 90 (2008) 1026-1039 D.P. Arya, Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery, Wiley-Interscience, Hoboken, NJ, (2007), 319 p. I. Charles, H. Xi, D.P. Arya, Sequence-specific targeting of RNA with an oligonucleotide-neomycin conjugate, Bioconjug. Chem. 18 (2007) 160-169 D. Arya, Diazo and Diazonium DNA Cleavage Agents: Studies on Model Systems and Natural Product Mechanisms of ActionTY - BOOK, (2006). B. Willis, D.P. Arya, Recognition of B-DNA by Neomycin-Hoechst 33258 Conjugates, Biochemistry. 45 (2006) 10217-10232 Hongjuan Xi, Sunil Kumar, Ljiljana Dosen-Micovic, Dev P. Arya.; Calorimetric and spectroscopic studies of aminoglycoside binding to AT-rich DNA triple helices, Biochimie, Volume 92, Issue 5, May 2010, Pages 514-529 S. Napoli, G.M. Carbone, C.V. Catapano, N. Shaw, D.P. Arya, Neomycin improves cationic lipid-mediated transfection of DNA in human cells, Bioorg. Med. Chem. Lett. 15 (2005) 3467-3469