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- Jabak, Adam A., et al.
(författare)
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Effect of Chirality on the Elastic Properties of the DNA-Threading Binuclear Ruthenium Complex
- 2020
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 118:3, Supplement 1, s. 617a-
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Konferensbidrag (refereegranskat)abstract
- Transition metal-based small molecules have been promising candidates for cancer treatments. A certain type of these molecules falls into a category known as threading intercalators, that have a dumbbell shape with a flat intercalating section in between bulky side chains. In order to bind to DNA, they must thread one of their bulky side chains through the DNA base pairs. The ruthenium-based molecule, ΛΛ-[μ-bidppz(phen)4Ru2]4+ (ΛΛ-P for short), is a transition metal-based threading intercalator. We use optical tweezers to study the interactions of ΛΛ-P with DNA to compare it with the previously studied ΔΔ-P, a complex that has the same chemical components but an opposite chirality. In these studies, we use the optical tweezers to trap a single DNA molecule and stretch it in the presence of various concentrations of ΛΛ-P. The DNA stretches obtained at saturated concentrations of ΛΛ-P at various forces allows us to obtain the effective elastic properties of the DNA-ΛΛ-P complex. This allows us to compare these properties to the previously studied ΔΔ-P complex to determine whether chirality has an effect. This type of comparison may lead us towards a better understanding of the role chirality has towards DNA binding.
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| 2. |
- Alizadehheidari, Mohammadreza, et al.
(författare)
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Nanoconfined Circular DNA
- 2014
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 274A-274A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nanofluidic channels have become a versatile tool to manipulate single DNA molecules. They allow investigation of confined single DNA molecules from a fundamental polymer physics perspective as well as for example in DNA barcoding techniques.
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| 3. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
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Unfolding of nanoconfined circular DNA
- 2015
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Ingår i: BIOPHYSICAL JOURNAL. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1, s. 231A-231A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Almaqwashi, A. A., et al.
(författare)
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Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation
- 2016
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 110:6, s. 1255-1263
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Tidskriftsartikel (refereegranskat)abstract
- DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [mu-dppzip(phen)(4)Ru-2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)(2)dppz) and the distal subunit (Ru(phen)(2)ip), respectively, each of which can be either right-handed (Delta) or left-handed (Lambda). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Delta x(eq), and the dynamic DNA structural deformations during ligand association x(on) and dissociation x(off). We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a K-d of 27 +/- 3 nM for (Delta,Lambda)-Piz to a K-d of 622 +/- 55 nM for (Lambda,Delta)-Piz. The striking affinity decrease is correlated with increasing Delta x(eq) from 0.30 +/- 0.02 to 0.48 +/- 0.02 nm and x(on) from 0.25 +/- 0.01 to 0.46 +/- 0.02 nm, but limited x(off) changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.
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| 10. |
- Fornander, Louise Helena, et al.
(författare)
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Using Nanofluidic Channels to Probe the Dynamics of Rad51-DNA Filaments
- 2014
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 106:2, s. 692A-693A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Rad51 is a key protein involved in the strand exchange reaction, a reaction where genetic material is transferred between two homologous DNA strands. Strand exchange is initiated by Rad51 forming a helical filament around single-stranded DNA (ssDNA), and the strand exchange is thereafter executed with a homologous double-stranded DNA (dsDNA). The structure of Rad51-DNA filaments, and also the activity of the strand exchange reaction, is dependent on the presence of ATP and dications, where Ca2+ has been shown to promote a higher degree of strand exchange than Mg2+.
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