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==NMR STUDY OF DNA (5'-D(*TP*GP*TP*AP*CP*A)-3') SELF-COMPLEMENTARY DUPLEX COMPLEXED WITH A BIS-DAUNORUBICIN WP-652, MINIMIZED AVERAGE STRUCTURE==
<StructureSection load='1amd' size='340' side='right'caption='[[1amd]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1amd]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AMD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BNR:BIS-DAUNORUBICIN'>BNR</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1al9|1al9]]</div></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1amd OCA], [https://pdbe.org/1amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1amd RCSB], [https://www.ebi.ac.uk/pdbsum/1amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1amd ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
In the search for new generations of anthracycline drugs, lower cytotoxic side effects and higher activity against resistant cancer cells are two major goals. A new class of bis-intercalating anthracycline drugs has been designed, synthesized, and shown to have promising activity against multidrug-resistant cells. Two daunorubicins symmetrically linked together via a p-xylenyl group, either at their N3' (compound WP631) or N4' sites (compound WP652), exhibit extraordinary DNA binding affinities. We have used high-resolution NRM studies to understand the DNA binding mode of these two new bis-daunorubicin anticancer compounds. The structures of the WP631-d(ACGTACGT)2 and the WP652-d(TGTACA)2 complexes have been determined by NOE-restrained refinement. WP631 binds strongly to the 5'-CG(A/T)(A/T)CG hexanucleotide sequence, with the aglycons intercalated between the two CpG sites at both ends of the hexanucleotide sequence. The overall conformation of the WP631-d(CGTACG)2 part is remarkably similar to the crystal structure of the 2:1 complex of daunorubicin and d(CGTACG)2, as predicted previously [Gao, Y.-G., &amp; Wang, A.H.H. (1996), J. Biomol. Struct. Dyn. 13, 103-117]. In contrast, the related bis-intercalator WP652 prefers the 5'-PyGTPu tetranucleotide sequence, with the aglycons intercalated between the PypG and TpPu sites. The binding of WP652 to DNA results in a severely distroted B-DNA duplex with the p-xylenyl tether moiety significantly protruded away from the bottom of the minor groove. While WP652 in some ways behaves similarly to other anticancer bis-intercalating antibiotics (e.g., triostine A and echinomycin), the detailed interactions between those two classes of bis-intercalators are quite different.

Binding of two novel bisdaunorubicins to DNA studied by NMR spectroscopy.,Robinson H, Priebe W, Chaires JB, Wang AH Biochemistry. 1997 Jul 22;36(29):8663-70. PMID:9289011<ref>PMID:9289011</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Robinson, H]]
[[Category: Wang, A H.J]]
[[Category: Bis-intercalator]]
[[Category: Daunorubicin]]
[[Category: Deoxyribonucleic acid]]
[[Category: Dna]]