Molecular Pharmacology of Intercalator-Groove Binder Hybrid Molecules

Bailly, Christian; Hénichart, Jean‐Pierre

doi:10.1007/978-1-349-13330-7_4

Cited by 8 publications

(8 citation statements)

References 120 publications

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“…56 Functionalized intercalators have previously demonstrated remarkable specificity for DNA targets. 57 For example, actinomycin D is a natural product that incorporates an intercalation domain fused to two cyclic peptide appendages that reside in the minor groove of DNA and give rise to its observed sequence selectivity. 58,59 Wilson and colleagues recognized this phenomenon and suggested that the specificity of any future RNA-directed intercalator would also require substituents that make extensive contacts in the RNA grooves as part of the intercalation complex.…”

Section: Rna Binding Of Intercalatorsmentioning

confidence: 99%

Recognition of double‐stranded RNA by proteins and small molecules

2003

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Molecular recognition of double-stranded RNA (dsRNA) is a key event for numerous biological pathways including the trafficking, editing, and maturation of cellular RNA, the interferon antiviral response, and RNA interference. Over the past several years, our laboratory has studied proteins and small molecules that bind dsRNA with the goal of understanding and controlling the binding selectivity. In this review, we discuss members of the dsRBM class of proteins that bind dsRNA. The dsRBM is an approximately 70 amino acid sequence motif found in a variety of dsRNA-binding proteins. Recent results have led to a new appreciation of the ability of these proteins to bind selectivity to certain sites on dsRNA. This property is discussed in light of the RNA selectivity observed in the function of two proteins that contain dsRBMs, the RNA-dependent protein kinase (PKR) and an adenosine deaminase that acts on dsRNA (ADAR2). In addition, we introduce peptide-acridine conjugates (PACs), small molecules designed to control dsRBM-RNA interactions. These intercalating molecules bear variable peptide appendages at opposite edges of an acridine heterocycle. This design imparts the potential to exploit differences in groove characteristics and/or base-pair dynamics at binding sites to achieve selective binding.

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Section: Rna Binding Of Intercalatorsmentioning

confidence: 99%

Recognition of double‐stranded RNA by proteins and small molecules

2003

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“…This goal can be achieved by construction of hybrid molecules composed of a polycyclic heteroaromatic chromophore, which can intercalate DNA or stabilize DNA-topoisomerase cleavable complex and an elastic chain containing heteroatoms as a DNA groove binder. 1 Some years ago, we found that indolo [2,3-b]quinolines exhibit significant cytotoxic activity. 2 These tetracyclic nitrogen heterocycles are the synthetically obtained analogs of naturally occurring neocryptolepine (I), an alkaloid isolated from roots of the African plant Cryptolepis sanguinolenta, which is used in traditional medicine for the treatment of infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Chemical shifts υ, given in ppm, were referenced against internal TMS. The spectrometer was equipped with an inverse 1 Hf 31 P 15 Ng 5 mm Nalorac probe with an actively shielded z-gradient coil (ID-PFG). Standard…”

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confidence: 99%

1H and13C NMR data for indolo[2,3-b]quinoline–aminoglycoside hybrids, a novel potent anticancer drug family

et al. 2006

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“…This knowledge permits the design and synthesis of hybrid molecules showing high DNA‐sequence selectivity. Such goal can be reached by introducing flexible chain containing heteroatoms into polycyclic heteroaromatic intercalator molecule …”

Section: Introductionmentioning

confidence: 99%

“…Such goal can be reached by introducing flexible chain containing heteroatoms into polycyclic heteroaromatic intercalator molecule. [6] Novel derivatives of indolo [2,3-b]quinoline, which consist of intercalating indoloquinoline core and attached alkylaminoalkyl chains, were obtained according to procedures described elsewere. [7] , [8] All the investigated indolo [2,3-b]quinolines were characterized by the presence of a planar, polycyclic chromophore, which is able to intercalate into DNA, and a basic side chain, which can increase DNA-binding affinity and also solubility under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%