PT-ACRAMTU, A Platinum–Acridine Anticancer Agent, Lengthens and Aggregates, but does not Stiffen or Soften DNA

Dutta, Samrat; Snyder, Matthew; Rosile, David; Binz, Kristen L.; Roll, Eric H.; Suryadi, Jimmy; Bierbach, Ulrich; Guthold, Martin

doi:10.1007/s12013-013-9614-8

Cited by 15 publications

(8 citation statements)

References 50 publications

(66 reference statements)

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“…6), 130 resulting in the lengthening and aggregation of DNA strands. 131 Multinuclear complexes Covalent binding. Platinum anticancer complexes consisting of two or more centres that are tethered together have been in development since the late 1980s.…”

Section: Mononuclear Complexesmentioning

confidence: 99%

Metal complex interactions with DNA

2015

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Increasing numbers of DNA structures are being revealed using biophysical, spectroscopic and genomic methods. The diversity of transition metal complexes is also growing, as the unique contributions that transition metals bring to the overall structure of metal complexes depend on the various coordination numbers, geometries, physiologically relevant redox potentials, as well as kinetic and thermodynamic characteristics. The vast range of ligands that can be utilised must also be considered. Given this diversity, a variety of biological interactions is not unexpected. Specifically, interactions with negatively-charged DNA can arise due to covalent/coordinate or subtle non-coordinate interactions such as electrostatic attraction, groove binding and intercalation as well as combinations of all of these modes. The potential of metal complexes as therapeutic agents is but one aspect of their utility. Complexes, both new and old, are currently being utilised in conjunction with spectroscopic and biological techniques to probe the interactions of DNA and its many structural forms. Here we present a review of metal complex-DNA interactions in which several binding modes and DNA structural forms are explored.

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Section: Mononuclear Complexesmentioning

confidence: 99%

Metal complex interactions with DNA

2015

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“…This method is very reliable when used on a large number of molecules. The second method 25,26 is based on the measurements of the angle between two small segments separated by a certain distance. This method does not require measurements on hundreds of molecules, and thus is advantageous for researchers who do not have a large number of molecules.…”

Section: Physical Analysismentioning

confidence: 99%

DNA-intercalator interactions: structural and physical analysis using atomic force microscopy in solution

2013

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DNA has a strong affinity for many heterocyclic aromatic dyes, such as acridine and its derivatives. Lerman in 1961 first proposed intercalation as the source of this affinity, and this mode of DNA binding has since attracted considerable research scrutiny. DNA intercalators (molecules that intercalate between DNA base pairs) have attracted particular attention due to their antitumoral activity and because they are widely used to fluorescently label DNA. The interaction between double-stranded DNA and bis-intercalators, such as the fluorescent dye YOYO-1 (dimer of oxazole yellow), has been widely studied. In the literature, there are contradicting data regarding the structure and the rigidity of the complex DNA-YOYO-1. Here, we address this problem using high-resolution atomic force microscopy in solution. We directly measured important structural parameters, such as the helical pitch and the elongation of the complex. By measuring intercalator-induced DNA elongation at different YOYO-1 concentrations, we determined the binding constant. We showed that intercalation induces distinct changes in the molecular elasticity compared to the free double stranded DNA. We found a decrease of the persistence length of DNA with increasing amount of bound YOYO-1, which contrasts with some previous assumptions. This study helps in understanding the physicochemical properties of bis-intercalators as well as the mechanism by which they interact with DNA and this technique can ultimately be applied to a large range of other DNA binding molecules such as anti-cancer or anti-viral drugs.

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“…[Pt(en)(ACRAMTU)Cl](NO 3 ) 2 (en = ethane-1,2-diamine; ACRAMTU = 1-[2- (acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) form covalent Pt–DNA bonds following thermal Cl − dissociation and the ACRAMTU ligand also intercalates between the DNA base pairs via the acridine moiety. This complex, with dual covalent and intercalative DNA interactions is effective against cisplatin-resistant cell lines [6,7], such that this type of binding motif may be useful in complexes that can be activated externally to enhance selectivity and reduce systemic toxicity.…”

Section: Introductionmentioning

confidence: 99%

Dual photoreactivity of a new Rh2(II,II) complex for biological applications

Akhimie

White

Turró

2017

Inorganica Chimica Acta

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A new Rh2(II,II) complex containing one dppn (benzo[i]dipyrido[3,2-a:2,3-c]phenazine) ligand with an extended π-system, cis-H,H-[Rh2(OCCH3NH)2(dppn)(CH3CN)2]2+ (2), was synthesized and characterized. The dppn ligand, which serves as a DNA base pair intercalator, chelates to a single Rh center and is positioned trans to the amidato N atoms of the bridging acetamide ligand. This ligand also possesses a low-lying dppn-centered 3ππ* state that is advantageous for the sensitization of singlet oxygen (1O2), which complex 2 produced with a quantum yield, Φ1O2 460, of 0.22(7) with 460 nm excitation. In addition, one equivalent of CH3CN is released from 2 upon irradiation with visible light, generating cis-H,H-[Rh2(OCCH3NH)2(dppn)(H2O)(CH3CN)]2+ in aqueous media with photoinduced ligand exchange quantum yield, ΦLE 450, of 0.0033(1). Thermal denaturation and relative viscosity studies are consistent with a π-stacking interaction of 2 with double-stranded DNA together with covalent binding to the duplex upon irradiation with visible light. Therefore, 2 exhibits dual photoreactivity towards DNA, making it potentially useful for photochemotherapy with enhanced activity relative to compounds able to achieve only one mode of cell death upon irradiation.

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PT-ACRAMTU, A Platinum–Acridine Anticancer Agent, Lengthens and Aggregates, but does not Stiffen or Soften DNA

Cited by 15 publications

References 50 publications

Metal complex interactions with DNA

Metal complex interactions with DNA

DNA-intercalator interactions: structural and physical analysis using atomic force microscopy in solution

Dual photoreactivity of a new Rh2(II,II) complex for biological applications

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