The DNA sequence specificity of cyanomorpholinoadriamycin

Cullinane, Carleen; Phillips, Don R.

doi:10.1016/0014-5793(91)81185-b

Cited by 9 publications

(9 citation statements)

References 13 publications

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“…While the latter might be ascribed to interstrand cross-links, the stops at C-C and G-G are more likely to result from intrastrand cross-links. Interestingly, such intrastrand cross-links efficiently inhibit elongation even when located on the nontranscribed strand. , …”

Section: E Anthracyclinesmentioning

confidence: 99%

“…44 However, due to steric reasons, only cisplatin (3) can form intrastrand cross-links on adjacent purines. Heat labile interstrand and intrastrand cross-links are formed by cyanomorpholinoadriamycin (10) 20,[45][46][47][48] and probably also by adriamycin in the presence of Fe(III) ions. 19 Vinyl chloride metabolites (32,33) form an additional ring on DNA bases (34,35,36).…”

Section: Covalent Adductsmentioning

confidence: 99%

“…144 The stops which are persistent under these conditions appear to correspond to interstand cross-links occurring between purines in the G-N-C/G-N-C or G-N-T/A-N-C sequences 144 (see also note 32). However, it has been reported that nitrogen mustard and other purine specific alkylating agents such as mephalan (44) and chlorambucil (45) induce transcription termination events that cannot be easily correlated with their sequence specificity. 161 Taq DNA pol 163 have been used to analyze the sequence specificity of nitrogen mustards (29) and mephalan (44).…”

Section: B Nitrogen Mustard and Its Bis-alkylating Congenersmentioning

confidence: 99%

“…Interestingly, such intrastrand cross-links efficiently inhibit elongation even when located on the nontranscribed strand. 45,46…”

Section: E Anthracyclinesmentioning

confidence: 99%

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The Effects of DNA Covalent Adducts on in Vitro Transcription

Gniazdowski

Cera

1996

Chem. Rev.

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Section: E Anthracyclinesmentioning

confidence: 99%

Section: Covalent Adductsmentioning

confidence: 99%

Section: B Nitrogen Mustard and Its Bis-alkylating Congenersmentioning

confidence: 99%

“…Interestingly, such intrastrand cross-links efficiently inhibit elongation even when located on the nontranscribed strand. 45,46…”

Section: E Anthracyclinesmentioning

confidence: 99%

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The Effects of DNA Covalent Adducts on in Vitro Transcription

Gniazdowski

Cera

1996

Chem. Rev.

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“…We have recently utilised an in vitro transcription assay to reveal the rapid and sequence specific binding of CMA to DNA (13,14). A preference of CMA binding at GG sequences was seen and appeared to reflect the formation of intrastrand crosslinks while binding at GC sites was of lower intensity and may represent interstrand crosslinks through adjacent guanine residues on opposite DNA strands (14).…”

Section: Introductionmentioning

confidence: 99%

Thermal stability of DNA adducts induced by cyanomorpholinoadriamycinin vitro

Cullinane

Phillips

1993

Nucl Acids Res

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The Adriamycin derivative, cyanomorpholinoadriamycin (CMA) was reacted with DNA in vitro to form apparent interstrand crosslinks. The extent of interstrand crosslink formation was monitored by a gel electrophoresis assay and maximal crosslinking of DNA was observed within 1 hr with 5 microM of drug. The interstrand crosslinks were heat labile, with a midpoint melting temperature of 70 degrees C (10 min exposure to heat) in 45% formamide. When CMA-induced adducts were detected as blockages of lambda-exonuclease, 12 blockage sites were observed with 8 being prior to 5'-GG sequences, one prior to 5'-CC, one prior to 5'-GC and 2 at unresolved combinations of these sequences. These exonuclease-detected blockages reveal the same sites of CMA-induced crosslinking as detected by in vitro transcription footprinting and primer-extension blockages on single strand DNA, where the blockages at 5'-GG and 5'-CC were identified as sites of intrastrand crosslinking and the 5'-GC blockage as a probable site of interstrand crosslinking. The thermal stability of both types of crosslink (10 min exposure to heat) ranged from 63-70 degrees C at individual sites. High levels of adduct were detected with poly (dG-dC) but not with poly (dI-dC). These results suggest adduct formation involving an aminal linkage between the 3 position of the morpholino moiety and N2 of guanine.

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Bis-daunomycin hydrazones: Interactions with DNA

et al. 1992

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A series of bis-daunomycin hydrazones were synthesised from diester diamide linking groups derived from alpha,omega-dicarboxylic acids. All members of the series bis-intercalated into DNA, as evidenced by doubling of the lengthening of rod-like DNA compared to daunomycin, and by a 1000-5000 fold slower dissociation from DNA than daunomycin under detergent sequestration conditions. The bis-hydrazones exhibited neighbour exclusion, and occupied 6 bp under saturating conditions of drug. A unique DNA sequence specificity was apparent from transcriptional footprinting of 100 bp of DNA, with the greatest preference for 5'-CACA sites.

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The DNA sequence specificity of cyanomorpholinoadriamycin

Cited by 9 publications

References 13 publications

The Effects of DNA Covalent Adducts on in Vitro Transcription

The Effects of DNA Covalent Adducts on in Vitro Transcription

Thermal stability of DNA adducts induced by cyanomorpholinoadriamycinin vitro

Bis-daunomycin hydrazones: Interactions with DNA

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