structural changes of zn(ii)bleomycin complexes when bound to dna hairpins containing the 5′-gt-3′ and 5′-gc-3′ binding sites, studied through nmr spectroscopy

structural changes of zn(ii)bleomycin complexes when bound to dna hairpins containing the 5′-gt-3′ and 5′-gc-3′ binding sites, studied through nmr spectroscopy

;Shelby E. Follett;Sally A. Murray;Azure D. Ingersoll;Teresa M. Reilly;Teresa E. Lehmann
tehnika 2017 Vol. 4 pp. 4-
339
follett2017magnetochemistrystructural

Abstract

We have previously investigated the diverse levels of disruption caused by Zn(II)BLMs with different C-termini to DNA hairpins containing 5′-GC-3′ and 5′-GT-3′ binding sites. The results of this investigation indicated that both the DNA-binding site and the bleomycin C-termini have an impact on the final conformation of the aforementioned hairpins in the drug-target complexes, as suggested by the different sets of intramolecular NOEs displayed by both oligonucleotides when bound to each Zn(II)BLM. The NMR signals elicited by 1H nuclei in the oligonucleotide bases and sugar moieties were also affected differently (shifted upfield or downfield in various patterns) depending on the BLM C-termini and the binding site in the oligonucleotides. The overall conclusion derived from the precedent research is that the spatial conformation of target DNA segments in DNA-Zn(II)BLM complexes could be forged by interactions between drug and DNA that are guided by the DNA binding site and the BLM C-termini. The present study focuses on the structural alterations exhibited by Zn(II)bleomycin-A2, -B2, -A5 and Zn(II)peplomycin molecules upon binding to the previously studied hairpins. Our main goal is to determine if different spatial conformations of the drugs in their DNA-bound forms are found in drug-DNA complexes that differ in the oligonucleotide binding site and BLM C-termini. Evidence that suggest that each Zn(II)bleomycin is structurally affected depending these two factors, as indicated by different sets of intramolecular NOE connectivities between drug protons and diverse patterns of shifting of their 1H-NMR signals, is provided.

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140099
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10.3390/magnetochemistry4010004
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