Identification of Trinucleotide Repeat Ligands with a FRET Melting Assay

Amrane, Samir; Cian, Anne De; Rosu, Frédéric; Kaiser, Markus; Pauw, Edwin De; Teulade-Fichou, Marie-Paule; Mergny, Jean‐Louis

doi:10.1002/cbic.200800062

Cited by 18 publications

(13 citation statements)

References 36 publications

(51 reference statements)

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“…An interesting methodological difference between DSF as applied to nucleic acids is that it typically uses FRET instead of the less specific dye binding phenomenon exploited in proteins, an approach which allows most of the nucleic acid target structure to remain intact and available for the small molecule to bind. Thus, FAM/TAMRA FRET pair has been utilized in T m measurement protocols in search of binders of various structural motifs, including in the context of high-throughput screening [24–27]. …”

Section: Experimental Setup and Data Interpretationmentioning

confidence: 99%

Recent developments in the use of differential scanning fluorometry in protein and small molecule discovery and characterization

Simeonov

2013

Expert Opinion on Drug Discovery

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Introduction Despite tremendous advances in the application of biophysical methods in drug discovery, the preponderance of instruments and techniques still require sophisticated analyses by dedicated personnel and/or large amounts of frequently hard-to-produce proteins. A technique which carries the promise of simplicity and relatively low protein consumption is the differential scanning fluorometry (DSF), wherein protein denaturation is monitored, through the use of environmentally sensitive fluorescent dye, in a temperature-ramp regime by observing the gradual exposure to the solvent of otherwise buried hydrophobic faces of protein domains. Areas covered This review describes recent developments in the field, with a special emphasis on advances published during the 2010–2013 period. Expert Opinion There has been a significant diversification of DSF applications beyond initial small molecule discovery into areas such as protein therapeutic development, formulation studies, and various mechanistic investigations, serving as a further indication of the broad penetration of the technique. In the small molecule arena, DSF has expanded towards sophisticated co-dependency MOA tests, demonstrating the wealth of information which the technique can provide. Importantly, the first public deposition of a large screening dataset may enable the use of thermal stabilization data in refining in silico models for small molecule binding.

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Section: Experimental Setup and Data Interpretationmentioning

confidence: 99%

Recent developments in the use of differential scanning fluorometry in protein and small molecule discovery and characterization

Simeonov

2013

Expert Opinion on Drug Discovery

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“…With regard to DNA binding, the CBIs present unique features that are (i) a strong association with DNA bases via aromatic π - π interactions and (ii) a very low affinity for duplex-DNA. This family of compounds has already been studied for its recognition of various unusual DNA structures, mainly mismatch-containing DNA [197–200], abasic sites [201], and trinucleotide repeats [202]. However, only two members of this family, namely, B O Q 1 (for Bis-Ortho-Quinacridine, Figure 13) [203–205] and BisA (for Bis-Acridine, Figure 13), [206] have been already evaluated for their ability to interact with quadruplex-DNA.…”

Section: Polyammonium Cyclophane-type Macrocyclesmentioning

confidence: 99%

“One Ring to Bind Them All”—Part I: The Efficiency of the Macrocyclic Scaffold for G‐Quadruplex DNA Recognition

Monchaud

Granzhan

Saettel

et al. 2010

Journal of Nucleic Acids

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Macrocyclic scaffolds are particularly attractive for designing selective G-quadruplex ligands essentially because, on one hand, they show a poor affinity for the “standard” B-DNA conformation and, on the other hand, they fit nicely with the external G-quartets of quadruplexes. Stimulated by the pioneering studies on the cationic porphyrin TMPyP4 and the natural product telomestatin, follow-up studies have developed, rapidly leading to a large diversity of macrocyclic structures with remarkable-quadruplex binding properties and biological activities. In this review we summarize the current state of the art in detailing the three main categories of quadruplex-binding macrocycles described so far (telomestatin-like polyheteroarenes, porphyrins and derivatives, polyammonium cyclophanes), and in addressing both synthetic issues and biological aspects.

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“…It is a very simple assay for determining the stabilizing effect of compounds on nucleic acid structures [24,25]. Similar procedures have been described to evaluate quadruplex binding compounds [26][27][28][29][30][31][32], triplex ligands [23] and trinucleotide repeat ligands [33]. This paper expands these assays to different nucleic acid secondary structures including: -d-G 3 (T 2 AG 3 ) 3 human telomere DNA quadruplex, -r-(C 3 UA 2 ) 2 C 3 :d-GT 2 AG 3 T 2 AG DNA:RNA duplex based on the short human telomere motif, -d-(GAA) 6 :(TTC) 6 duplex related to Friedreich ataxia and -d-(CTG) 7 hairpin related to myotonic dystrophy type 1.…”

Section: Introductionmentioning

confidence: 99%