Isohelicity and Strand Selectivity in the Minor Groove Binding of Chiral (1R,2R)- and (1S,2S)-Bis(netropsin)-1,2-cyclopropanedicarboxamide Ligands to Duplex DNA

Singh, Meghna; Plouvier, Bertrand; Hill, G. Craig; Gueck, Juergen; Pon, Richard T.; Lown, J. William

doi:10.1021/ja00095a002

Cited by 38 publications

(21 citation statements)

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“…It was shown that when two netropsin molecules are linked through a chiral spacer (such as trans-1,2-cyclopropandioic acid), the resulting dimer is able to bind to an extended DNA region, with binding modes and stabilities depending on the stereochemistry of the linker. 29 Following this model, polyamides constituted by achiral N-methylpyrrole or N-methylimidazole containing amino acids, developed by Dervan,30 are very effective DNA binding molecules through minor groove interactions, and have reached binding affinities and selectivities comparable to those of DNA binding proteins; the molecular basis of this selectivity has been clarified at the molecular level through structural characterization, and is based on the scheme reported in the Figure 3b,d. 31,32 Since the most effective binding is performed by two molecules of polyamide interacting with the same tract of the DNA minor groove, with the selectivity being dictated by the ; (d) additional GC recognition scheme; (e) hairpin polyamides containing a achiral g-aminobutyric or a chiral 2,4-diaminobutyric acid spacer; (f) main recognition scheme for a hairpin polyamide containg a (R)-enantiomer linker with ''forward'' orientation, as evaluated by Fe(EDTA) mediated strand scission (vertical bars indicate the extend of cleavage at a specific site) 33 ; (f) recognition scheme of the (R)-enantiomer and (g) ''reverse'' orientation for the (S)-enantiomer linker (vertical bars represent sensitivity to Fc(II) mediated cleavage).…”

Section: Minor Groove Binding Moleculesmentioning

confidence: 99%

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

et al. 2007

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The understanding of the interaction of chiral species with DNA or RNA is very important for the development of new tools in biology and of new drugs. Several cases in which chirality is a crucial point in determining the DNA binding mode are reviewed and discussed, with the aim of illustrating how chirality can be considered as a tool for improving the understanding of mechanisms and the effectiveness of nucleic acid recognition. The review is divided into two parts: the former describes examples of chiral species interacting with DNA: intercalators, metal complexes, and groove binders; the latter part is dedicated to chirality in DNA analogs, with discussion of phosphate stereochemistry and chirality of ribose substitutes, in particular of peptide nucleic acids (PNAs) for which a number of works have been published recently dealing with the effect of chirality in DNA recognition. The discussion is intended to show how enantiomeric recognition originates at the molecular level, by exploiting the enormous progresses recently achieved in the field of structural characterization of complexes formed by nucleic acid with their ligands by crystallographic and spectroscopic methods. Examples of application of the DNA binding molecules described and the role of chirality in DNA recognition relevant for biotechnology or medicinal chemistry are reported.

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Section: Minor Groove Binding Moleculesmentioning

confidence: 99%

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

et al. 2007

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“…In long pyrrole-imidazole polyamides, however, a slight mismatch between the contour length of the polyamide and the contour length of the DNA minor groove causes the rings to get ''out of phase,'' and binding does not improve for polyamides with greater than Ϸ5 units (17). This issue has been addressed previously in connection with polyamide design (18), and methods have been reported to restore proper phasing by incorporating spacers into long polyamides (19). Hence, the effects of phasing mismatch will be neglected in this work.…”

Section: Methodsmentioning

confidence: 99%

The theoretical limits of DNA sequence discrimination by linked polyamides

Walker

Landaw²,

Dickerson³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Linked polyamides bind in the minor groove of double-stranded DNA in a partially sequence-specific manner. This report analyzes the theoretical limits of DNA sequence discrimination by linked polyamides composed of two to four different types of heterocyclic rings, determining (i) the optimal choice of base-binding specificity for each ring and (ii) the optimal design for a polyamide composed of these rings to target a given DNA sequence and designed to maximize the fraction of the total polyamide binding to the specified target sequence relative to all other sequences. The results show that, fortuitously, polyamides composed of pyrrole, a naturally occurring G-excluding element, and imidazole, a rationally designed G-favoring element, have features similar to the theoretical optimum design for polyamides composed of two different rings. The results also show that, in polyamides composed of two or three types of heterocyclic rings, choosing a nonspecific ''placeholder'' ring, which binds equally strongly to each of the four bases, along with one or two base-specific rings will often enhance sequence specificity over a polyamide composed entirely of base-specific rings.

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“…The 1 H NMR resonances of the free oligonucleotides were assigned by standard techniques, using NOESY and DQF COSY spectra [31][32][33]. In 90% H 2 O-10% D 2 O solution, four imino resonances were observed for d(CGCGATCGCG) 2 and five imino resonances for d(GCGCTTAAGCGC) 2 at 25°C.…”

Section: Assignment Of the Proton Resonances Of The Free Oligonucleotmentioning

confidence: 99%

Synthesis and characterization of the diastereomers Λ- and Δ-[Ru(bpy)2(m-bpy-l-Arg-Gly-l-Asn-l-Ala-l-His-l-Glu-l-Arg)]Cl2

Myari¹,

Hadjiliadis²,

Garoufis³

2005

Journal of Inorganic Biochemistry

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Isohelicity and Strand Selectivity in the Minor Groove Binding of Chiral (1R,2R)- and (1S,2S)-Bis(netropsin)-1,2-cyclopropanedicarboxamide Ligands to Duplex DNA

Cited by 38 publications

References 0 publications

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

Chirality as a tool in nucleic acid recognition: Principles and relevance in biotechnology and in medicinal chemistry

The theoretical limits of DNA sequence discrimination by linked polyamides

Synthesis and characterization of the diastereomers Λ- and Δ-[Ru(bpy)2(m-bpy-l-Arg-Gly-l-Asn-l-Ala-l-His-l-Glu-l-Arg)]Cl2

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