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oai:www.ideals.illinois.edu:2142/85497 2023-07-11 col_2142_5131 col_2142_14828 com_2142_5130 com_2142_14827 com_2142_14793 com_2142_8903

Wang, Andrew H.J. Yang, Xianglei 2015-09-25T22:46:17Z 2015-09-25T22:46:17Z 10000-01-01 2000 2000 T:G mismatched base pair is associated with many genetic mutations. Understanding its biological consequences can be aided by studying the structural perturbation of DNA caused by T:G base pair and by specific probing of the mismatch using small molecular ligands. We have shown that AR-1-144, a tri-imidazole minor groove binder, recognizes the CCGG sequence. The NMR structural analysis of the symmetric 2:1 complex of AR-1-144 and GAACCGGTTC revealed that each AR-1-144 binds to four base pairs with the guanine N2 amino group forming a bifurcated hydrogen bond to a side-by-side Im/Im pair. We then predicted that the free G-N2 amino group in a T:G wobble base pair can form two individual hydrogen bonds to a side-by-side Im/Im pair. Thus an Im/Im pair may be a good recognition motif for a T:G base pair in DNA. The cooperative and tight binding of an AR-1-144 homo-dimer to GAA CTGGTTC permits a detailed structural analysis by 2D-NOE NMR refinement and the refined structure confirms our prediction. Surprisingly, AR-1-144 does not bind to GAATCGGTTC. We further show that both the Im-Im-Im/Im-Py-Im hetero-dimer and the Im-Im-Im/Im-Im-Im homo-dimer bind strongly to the CACGG&barbelow;GTC+GACT&barbelow;CGTG duplex. These results suggest that an Im/Im pair can specifically recognize a single T:G mismatch. Together with other sequence-specific recognition rules, our results may be useful in future design of drugs that can recognize and act on a certain gene sequence specifically. Made available in DSpace on 2015-09-25T22:46:17Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 9971228.pdf: 5468855 bytes, checksum: e10b4666369f82b7e77c3bfc9c76724c (MD5) Previous issue date: 2000 Embargo set by: Seth Robbins for item 86778 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 123 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2000. http://hdl.handle.net/2142/85497 (MiAaPQ)AAI9971228 eng Biology, Molecular Probing Non-Canonical DNA Structures With Anticancer Drugs text University of Illinois at Urbana-Champaign Dissertation Ph.D. Biophysics and Computational Biology Biophysics and Computational Biology