Functionalized head-to-head hairpin polyamides: Synthesis, double-stranded DNA-binding activity and affinity

Halby, Ludovic; Ryabinin, V. A.; Sinyakov, A. N.; Boutorine, Alexandre S.

doi:10.1016/j.bmcl.2005.05.106

Cited by 14 publications

(14 citation statements)

References 17 publications

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“…dHP must be considered as two HPs joined together by a linker (see Scheme 1). The disposition and the orientation of the ligands in the DNA minor groove are hypothetical but in the place where two HPs can fit, only one dHP can fit logically, as observed by MS. As expected from the value of K d determined by gel shift studies [40] ( ∼6 nM), the complex ions were observed in large amounts in excess when compared to free DNA. These results strongly support the fact that gas-phase complexes keep their solution properties.…”

Section: Resultsmentioning

confidence: 64%

“…DNA sequences targeted by dHP are indicated in bold. These values previously reported elsewhere [40] have been determined in solution by gel electrophoresis.…”

Section: Experimental Section Materialsmentioning

confidence: 99%

“…HP hairpin polyamide ligand (Scheme 1) containing six N-methylpyrrole rings was kindly provided by Drs A. Sinyakov and V. Ryabinin (Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia). dHP double hairpin polyamide was prepared by previously reported protocol [40] followed by removal of the Boc (tert-butyloxycarbonyl) protection from the CP62 synthesis product. Polyamides were dissolved in DMSO; then methanol and water were added to reach 500 µM in DMSO/MeOH/H 2 O (5/45/50 V/V).…”

Section: Experimental Section Materialsmentioning

confidence: 99%

“…All of them contain a series of adenine or thymine (in bold), which are targeted by the ligand dHP. K d values were independently determined by gel electrophoresis from a ligand analogous to dHP (dHP with central nitrogen atom substituted by a Boc-aminopropyl group) with dsDNA containing the same target sequences [40] . The affinity of the ligand increases from the dsDNA 'A' to the dsDNA 'C' (K dA ≈ 56 nM, K dB ≈ 29 nM; K dC ≈ 6.2 nM, see Scheme 2).…”

Section: Affinity Of the Dhp Ligand Against Two Different Dsdna Sequementioning

confidence: 99%

“…Recently, new head-to-head bis-hairpin MGBs were described with higher affinity for dsDNA and sequence specificity up to 10-12 base pairs. [40] Yuan and coworkers [41 -45] published a series of papers on the analysis of noncovalent complexes of dsDNA with hairpin polyamides containing up to eight rings. The authors sorted the affinity of various polyamides against dsDNA by studying the effect of the molar ratio (dsDNA to polyamides) on binding or from competition studies.…”

Section: Introductionmentioning

confidence: 99%

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A new method for the determination of the relative affinity of a ligand against various DNA sequences by electrospray ionization mass spectrometry. Application to a polyamide minor groove binder

Buchmann¹,

Boutorine²,

Halby³

et al. 2009

J. Mass Spectrom.

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A new method for the determination of the relative affinity of a ligand against various dsDNA sequences is presented by using electrospray ionization time-of-flight mass spectrometry (ESI-QTOF) mass spectrometry. The principle is described here through the complexation of double-stranded DNA by a polyamide ligand including twelve N-methylpyrrole rings. However this method could be applied to other ligands especially when dissociation constants (Kd) are in nanomolar range. This method does not require knowing the ligand concentration accurately. It allows determination of the relative affinity of a ligand against various dsDNA sequences for 1 : 1 complex stoichiometries in a quick manner without labeling.

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Section: Resultsmentioning

confidence: 64%

“…DNA sequences targeted by dHP are indicated in bold. These values previously reported elsewhere [40] have been determined in solution by gel electrophoresis.…”

Section: Experimental Section Materialsmentioning

confidence: 99%

Section: Experimental Section Materialsmentioning

confidence: 99%

Section: Affinity Of the Dhp Ligand Against Two Different Dsdna Sequementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A new method for the determination of the relative affinity of a ligand against various DNA sequences by electrospray ionization mass spectrometry. Application to a polyamide minor groove binder

Buchmann¹,

Boutorine²,

Halby³

et al. 2009

J. Mass Spectrom.

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Triplex‐Forming Twisted Intercalating Nucleic Acids (TINAs): Design Rules, Stabilization of Antiparallel DNA Triplexes and Inhibition of G‐Quartet‐Dependent Self‐Association

2011

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The majority of studies on DNA triple helices have been focused on pH-sensitive parallel triplexes with Hoogsteen CT-containing third strands that require protonation of cytosines. Reverse Hoogsteen GT/GA-containing antiparallel triplex-forming oligonucleotides (TFOs) do not require an acidic pH but their applicability in triplex technology is limited because of their tendency to form undesired highly stable aggregates such as G-quadruplexes. In this study, G-rich oligonucleotides containing 2-4 insertions of twisted intercalating nucleic acid(TINA) monomers are demonstrated to disrupt the formation of G-quadruplexes and form stable antiparallel triplexes with target DNA duplexes. The structure of TINA-incorporated oligonucleotides was optimized, the rules of their design were established and the optimal triplex-forming oligonucleotides were selected. These oligonucleotides show high affinity towards a 16 bp homopurine model sequence from the HIV-1 genome; dissociation constants as low as 160 nM are observed whereas the unmodified TFO does not show any triplex formation and instead forms an intermolecular G-quadruplex with T(m) exceeding 90°C in the presence of 50 mM NaCl. Here we present a set of rules that help to reach the full potential of TINATFOs and demonstrate the effect of TINA on the formation and stability of triple helical DNA.

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Polyamide Fluorescent Probes for Visualization of Repeated DNA Sequences in Living Cells

et al. 2015

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DNA imaging in living cells usually requires transgenic approaches that modify the genome. Synthetic pyrrole-imidazole polyamides that bind specifically to the minor groove of double-stranded DNA (dsDNA) represent an attractive approach for in-cell imaging that does not necessitate changes to the genome. Nine hairpin polyamides that target mouse major satellite DNA were synthesized. Their interactions with synthetic target dsDNA fragments were studied by thermal denaturation, gel-shift electrophoresis, circular dichroism, and fluorescence spectroscopy. The polyamides had different affinities for the target DNA, and fluorescent labeling of the polyamides affected their affinity for their targets. We validated the specificity of the probes in fixed cells and provide evidence that two of the probes detect target sequences in mouse living cell lines. This study demonstrates for the first time that synthetic compounds can be used for the visualization of the nuclear substructures formed by repeated DNA sequences in living cells.

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Functionalized head-to-head hairpin polyamides: Synthesis, double-stranded DNA-binding activity and affinity

Cited by 14 publications

References 17 publications

A new method for the determination of the relative affinity of a ligand against various DNA sequences by electrospray ionization mass spectrometry. Application to a polyamide minor groove binder

A new method for the determination of the relative affinity of a ligand against various DNA sequences by electrospray ionization mass spectrometry. Application to a polyamide minor groove binder

Triplex‐Forming Twisted Intercalating Nucleic Acids (TINAs): Design Rules, Stabilization of Antiparallel DNA Triplexes and Inhibition of G‐Quartet‐Dependent Self‐Association

Polyamide Fluorescent Probes for Visualization of Repeated DNA Sequences in Living Cells

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