A peptide-acridine conjugate with ribonucleolytic activity

Tung, Ching–Hsuan; Ebright, Yon W.; Shen, Xueyu; Stein, Stanley J.

doi:10.1016/s0960-894x(01)80205-5

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…Intercalators are very useful for the delivery of small peptides to DNA and RNA ( − ), and several groups have successfully applied intercalators to the design of artificial nucleases. For example, an active tetrapeptide was attached to an acridine intercalator, and the histidine residues were found to promote RNA cleavage ( , ). More recently, using a strategy very similar to our own, a peptide with unnatural zinc-coordinating residues was delivered to DNA by conjugation with acridine ().…”

Section: Discussionmentioning

confidence: 99%

DNA Hydrolysis and Oxidative Cleavage by Metal-Binding Peptides Tethered to Rhodium Intercalators

et al. 2001

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With the goal of developing artificial nucleases for DNA hydrolysis, metal-coordinating peptides have been tethered to a DNA-intercalating rhodium complex to deliver metal ions to the sugar-phosphate backbone. The intercalator, [Rh(phi)(2)bpy']Cl(3) [phi = 9,10-phenanthrenequinone diimine; bpy' = 4-(butyric acid)-4'-methyl-2,2'-bipyridine], provides DNA binding affinity, and a metal-binding peptide contributes reactivity. This strategy for DNA hydrolysis is a general one, and zinc(II)-promoted cleavage has been demonstrated for two widely different tethered metallopeptides. An intercalator coupled with a de novo-designed alpha helix containing two histidine residues has been demonstrated to cleave both supercoiled plasmid and linear DNA substrates. Mutation of this peptide confirms that the two histidine residues are essential for Zn(2+) binding and cleavage. Zinc(II)-promoted cleavage of supercoiled plasmid has also been demonstrated with an intercalator-peptide conjugate containing acidic residues and modeled after the active site of the BamHI endonuclease. Other redox-active metals, such as copper, have been delivered to DNA with our intercalator-peptide conjugates to effect oxidative chemistry. Copper cleavage experiments and photocleavage experiments with [Rh(phi)(2)bpy'](3+) complement the hydrolysis studies and provide structural information about the interactions between the tethered metallopeptides and DNA. Variation of the rhodium intercalator was also explored, but with a mismatch-specific intercalator, no site-specific hydrolysis was found. These experiments, in which the peptide, the metal cation, and the intercalator components of the conjugate are each varied, illustrate some of the issues involved in creating an artificial nuclease with DNA intercalators and metallopeptides.

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Section: Discussionmentioning

confidence: 99%

DNA Hydrolysis and Oxidative Cleavage by Metal-Binding Peptides Tethered to Rhodium Intercalators

et al. 2001

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“…Since our review is aimed to 9-nitrogen containing compounds, the papers dealing with a binding of acridine-9-carboxylic acid [74][75][76][77][78][79][80][81] and acridine-9-carboxaldehyde [82][83][84] to amino group containing compounds and utilization of -(acridin-9-yl) alanine [85] were omitted.…”

Section: Syntheses Of 9-aminoacridines and Their Conjugatesmentioning

confidence: 99%

“…The several other 9-aminoacridine containing RNA nucleases were described, however, the 9-position was substituted either with carboxyl [77] or aldehyde [82][83][84].…”

Section: Mono-intercalatorsmentioning

confidence: 99%

A Role of the 9-Aminoacridines and their Conjugates in a Life Science

Šebestı́k¹,

Hlaváček²,

Stibor

2007

CPPS

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The 9-aminoacridines play an important role in medicine. They were applied first in a treatment of protozoal infections in the beginning of the last century. Recently, it has been shown that the 9-aminoacridines are successful candidates for treatment of cancer, viral and prion diseases. Their conjugation with biomolecules such as peptides and proteins may modulate their activity, bioavailability and applicability. This review deals with the synthesis of 9-aminoacridine, its conjugation with variety of molecules and utilization of such conjugates in several fields of science.

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“…Acridine occurs in a large number of natural products and attracts a great deal of attention because of its wide range of biological activities. Its derivatives produce remarkable effects as pharmaceuticals, including antibacterial, anticancer, , antitumor, , ribonucleolytic, antiangiogenic, and antifungicidal activities. It is well-known that the three-component reaction of arylamine, aromatic aldehyde, and cyclic 1,3-dicarbonyl compound is an efficient method for synthesizing these potentially active heterocycles .…”

Section: Introductionmentioning

confidence: 99%

Combinatorial Synthesis of Pyrrolo[3,2-f]quinoline and Pyrrolo[3,2-a]acridine Derivatives via a Three-Component Reaction under Catalyst-Free Conditions

Zhou

Chen

et al. 2013

ACS Comb. Sci.

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A combinatorial synthesis of pyrrolo[3,2-f]quinoline and pyrrolo[3,2-a]acridine derivatives is described as a three-component reaction of aromatic aldehyde, 1H-indol-5-amine, and 1,3-dicarbonyl compounds under catalyst-free conditions. The 1,3-dicarbonyl compounds include 5,5-dimethylcyclohexane-1,3-dione, cyclopentane-1,3-dione, and 2H-indene-1,3-dione. It is interesting that the designed reactions gave aromatized or unaromatized products, which depend on the reaction temperature and reactants of 1,3-dicarbonyl compounds.

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A peptide-acridine conjugate with ribonucleolytic activity

Cited by 8 publications

References 15 publications

DNA Hydrolysis and Oxidative Cleavage by Metal-Binding Peptides Tethered to Rhodium Intercalators

DNA Hydrolysis and Oxidative Cleavage by Metal-Binding Peptides Tethered to Rhodium Intercalators

A Role of the 9-Aminoacridines and their Conjugates in a Life Science

Combinatorial Synthesis of Pyrrolo[3,2-f]quinoline and Pyrrolo[3,2-a]acridine Derivatives via a Three-Component Reaction under Catalyst-Free Conditions

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