Surprising duplex stabilisation upon mismatch introduction within triply modified duplexes

Catry, Mieke A.; Gheerardijn, Vicky; Madder, Annemieke

doi:10.1016/j.bioorg.2010.01.002

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…Here, histamine is tethered to the C5 of thymidine via an amide bond, placing the imidazole function in the major groove. Only minimal disruption of the helical structure is expected, in contrast with, for instance, modifications at the C2′ of the ribose sugar ( 50 ). This is validated from the MD results described further.…”

Section: Resultsmentioning

confidence: 99%

Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

Buyst

Gheerardijn

Fehér

et al. 2014

Nucleic Acids Research

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The predictable 3D structure of double-stranded DNA renders it ideally suited as a template for the bottom-up design of functionalized nucleic acid-based active sites. We here explore the use of a 14mer DNA duplex as a scaffold for the precise and predictable positioning of catalytic functionalities. Given the ubiquitous participation of the histidine-based imidazole group in protein recognition and catalysis events, single histidine-like modified duplexes were investigated. Tethering histamine to the C5 of the thymine base via an amide bond, allows the flexible positioning of the imidazole function in the major groove. The mutual interactions between the imidazole and the duplex and its influence on the imidazolium pKaH are investigated by placing a single modified thymine at four different positions in the center of the 14mer double helix. Using NMR and unrestrained molecular dynamics, a structural motif involving the formation of a hydrogen bond between the imidazole and the Hoogsteen side of the guanine bases of two neighboring GC base pairs is established. The motif contributes to a stabilization against thermal melting of 6°C and is key in modulating the pKaH of the imidazolium group. The general features, prerequisites and generic character of the new pKaH-regulating motif are described.

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Section: Resultsmentioning

confidence: 99%

Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

Buyst

Gheerardijn

Fehér

et al. 2014

Nucleic Acids Research

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“…One can further imagine that introduction of extra functionalities can have an impact on the duplex stability and final structure of the double helix. This was illustrated in previous research in our laboratory where introduction of modified nucleosides on the 2’-position in a DNA double helix resulted in a destabilization of the duplex of 5 °C per modified unit [32]. Although this destabilization depends on many different aspects, such as the type and length of the linker and the position of the modification, it is important to minimize destabilization as much as possible, more specifically when introduction of more than one modification is desired.…”

Section: Introductionmentioning

confidence: 88%

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

Gheerardijn

Begin

Madder

2014

Beilstein J. Org. Chem.

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SummaryFunctionalized oligonucleotides have recently gained increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional group, we present here a straightforward method for direct linking of functionalized amino acids to the nucleoside base, thus equipping the nucleoside with two extra functionalities at once. As a proof of principle, we have introduced three amino acids with functional groups frequently used as key-intermediates in DNA- and RNAzymes via an efficient and straightforward domino carboxamidation reaction.

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“…However, only Madder's team developed 2 ′functionalized deoxyuridine phosphoramidites 14, 15, and 16 bearing amino acid side chain-like residues such as suitably protected carboxylic acid, imidazole, and alcohol functions, respectively, which were tethered to the oligonucleotide via an amide bond (Figure 5) [64]. After solid-phase synthesis, up to three modifications could be introduced by strand, and the rigid but programable duplex structure was used to organize the residues along the major groove of the helix to obtain up to six different sequences, which were then combined into their corresponding duplexes [65]. Analysis of the thermal denaturation studies indicated that each introduction has a negative impact of −5 °C on the thermal value, although one mismatched duplex displayed a ∆Tm of −5.3 °C (compared to an expected ∆Tm of ≈−15 °C), compensating and largely overcoming the destabilization Scheme 4.…”

Section: Functionalized Oligonucleotides As Serine Protease Mimicsmentioning

confidence: 99%

Functionalized oligonucleotides, synthetic catalysts as enzyme mimics

Chardet,

Serres,

Payrastre

et al. 2024

Comptes Rendus. Chimie

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This review describes the chemical rationale behind the modification of deoxyribonucleotides, which are later incorporated through an enzymatic or automated supported process, resulting in the synthesis of functionalized oligonucleotides (FuON). These additional handles (located on the base or the sugar moiety) were carefully chosen to enhance the rather limited repertoire of DNA to develop FuONs that display enzyme-like properties such as catalysis and recognition. We will exemplify the development of FuON either presenting RNA-cleaving activity or acting as peroxidase or protease mimics and discuss the impact of the introduced modifications.

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Surprising duplex stabilisation upon mismatch introduction within triply modified duplexes

Cited by 4 publications

References 46 publications

Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

Identification of a pKa-regulating motif stabilizing imidazole-modified double-stranded DNA

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

Functionalized oligonucleotides, synthetic catalysts as enzyme mimics

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