Unique base-step recognition by a platinum-acridinylthiourea conjugate leads to a DNA damage profile complementary to that of the anticancer drug cisplatin

Biochemistry
Michael E BudimanUlrich Bierbach

Abstract

The sequence specificity and time course of covalent DNA adduct formation of the novel platinum-acridine conjugate [PtCl(en)(ACRAMTU)](NO(3))(2) [PT-ACRAMTU, 2; en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea] have been investigated using restriction enzyme cleavage and transcription footprinting assays and compared to the damage produced by the clinical agent cis-diamminedichloroplatinum(II) (cisplatin, 1). The rate of DNA binding of 1 and 2 was also monitored by atomic emission spectrometry. Restriction enzymes were chosen that cleave the phosphodiester linkage at, or adjacent to, the predicted damage sites. While conjugate 2 selectively protected supercoiled plasmid from cleavage by EcoRI and DraI enzymes at their respective restriction sites, G downward arrow AATTC and TTT downward arrow AAA, 1 inhibited DNA hydrolysis by HindIII and PspOMI at A downward arrow AGCTT and G downward arrow GGCCC (arrows mark cleavage sites) more efficiently. Transcription footprinting using T7 RNA polymerase revealed major single-base damage sites for 2 at adenine in 5'-TA and 5'-GA sequences. In addition, the enzyme is efficiently stalled at guanine bases, primarily in the sequence 5'-CGA where the damag...Continue Reading

References

Mar 6, 2003·Bioorganic & Medicinal Chemistry Letters·Todd M AugustusUlrich Bierbach
Mar 17, 2004·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Hemanta Baruah, Ulrich Bierbach

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Citations

Nov 19, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jayati Roy ChoudhuryUlrich Bierbach
Nov 18, 2008·Journal of Medicinal Chemistry·Zhidong MaUlrich Bierbach
Jun 29, 2010·Chemical Research in Toxicology·Lu RaoUlrich Bierbach
Sep 30, 2005·Nucleic Acids Research·Jayati Roy Choudhury, Ulrich Bierbach
May 16, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Hieronimus W KavaVincent Murray
Feb 23, 2008·Chemistry : a European Journal·Seniz Ozalp-YamanJan Reedijk
Sep 19, 2012·Chemistry : a European Journal·Jimmy Suryadi, Ulrich Bierbach
Apr 26, 2016·Chemistry : a European Journal·Imogen A RiddellStephen J Lippard
Apr 4, 2017·Journal of Applied Toxicology : JAT·Mária KožurkováPavol Kristian
Dec 14, 2018·Inorganic Chemistry·Xiyuan YaoUlrich Bierbach

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