1,8-Naphthyridin-2(1H)-ones − Novel Bicyclic and Tricyclic Analogues of Thymine in Peptide Nucleic Acids (PNAs)

Eldrup, Anne B.; Nielsen, Bettina Bryde; Haaima, Gerald; Rasmussen, Hanne B.; Kastrup, J.S.; Christensen, Claus Bo Vöge; Nielsen, Peter E.

doi:10.1002/1099-0690(200105)2001:9<1781::aid-ejoc1781>3.0.co;2-k

Cited by 61 publications

(75 citation statements)

References 31 publications

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“…Water molecules located in the minor groove are also stabilized by H-bonds with nucleobases (purine-N3 or pyrimidine O2). In particular, those bound to the PNA strand form a bridge between the nucleobases and the amides of the backbone (N or O depending on the orientation of the amide bond), as observed for the PNA-PNA structure (11)(12)(13).…”

Section: Resultsmentioning

confidence: 99%

“…A PNA-RNA duplex (8) and a PNA-DNA duplex (9) were characterized by NMR in solution, whereas a (PNA) 2 -DNA triplex (10) and three PNA-PNA duplexes (11)(12)(13) were solved by x-ray crystallography. The structural analysis in solution of the PNA-DNA (9) and PNA-RNA duplexes (8) showed that PNA, when hybridized to RNA, adopts an A-like helix, whereas, when hybridized to a complementary DNA strand, it adopts a conformation that is different from both the A and the B forms.…”

mentioning

confidence: 99%

“…The crystal structure of the (PNA) 2 -DNA triplex (10) also showed helical parameters significantly different from those of canonical DNA or RNA helical forms, defining a type of helix, named the P-helix, characterized by a small twist angle, a large x-displacement, and a wide, deep major groove. Finally, structural features of the PNA-PNA double helix (11)(12)(13) are similar to those of the P-helix mentioned above.…”

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confidence: 99%

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Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Menchise

Simone

Tedeschi

et al. 2003

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

151

164

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Peptide nucleic acids (PNAs) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton. They bind DNA and RNA with high specificity and selectivity, leading to PNA-RNA and PNA-DNA hybrids more stable than the corresponding nucleic acid complexes. The binding affinity and selectivity of PNAs for nucleic acids can be modified by the introduction of stereogenic centers (such as D-Lys-based units) into the PNA backbone. To investigate the structural features of chiral PNAs, the structure of a PNA decamer containing three D-Lys-based monomers (namely H-GpnTpnApnGpnAdlTdlCdlApnCpnTpn-NH2, in which pn represents a pseudopeptide link and dl represents a D-Lys analogue) hybridized with its complementary antiparallel DNA has been solved at a 1.66-Å resolution by means of a single-wavelength anomalous diffraction experiment on a brominated derivative. The D-Lys-based chiral PNA-DNA (LPD) heteroduplex adopts the so-called P-helix conformation. From the substantial similarity between the PNA conformation in LPD and the conformations observed in other PNA structures, it can be concluded that PNAs possess intrinsic conformational preferences for the P-helix, and that their flexibility is rather restricted. The conformational rigidity of PNAs is enhanced by the presence of the chiral centers, limiting the ability of PNA strands to adopt other conformations and, ultimately, increasing the selectivity in molecular recognition. P eptide nucleic acids (PNAs) are oligonucleotide mimics in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton, composed of N-(2-aminoethyl)glycine units (1) (Fig. 1). Nucleobases are linked to this skeleton through a two-atom carboxymethyl spacer.PNAs bind DNA and RNA with high specificity and selectivity, forming Watson-Crick base pairs and leading to PNA-RNA and PNA-DNA hybrids that are more stable than the corresponding nucleic acid complexes (2). Because of their high thermal stability and resistance to proteases and nucleases, PNAs are ideal candidates as antisense or antigene therapeutic agents (3-6) and are currently used as powerful tools in molecular biology and in diagnostics (7).Three-dimensional structures have been determined for the major families of PNA complexes by different techniques. A PNA-RNA duplex (8) and a PNA-DNA duplex (9) were characterized by NMR in solution, whereas a (PNA) 2 -DNA triplex (10) and three PNA-PNA duplexes (11-13) were solved by x-ray crystallography. The structural analysis in solution of the PNA-DNA (9) and PNA-RNA duplexes (8) showed that PNA, when hybridized to RNA, adopts an A-like helix, whereas, when hybridized to a complementary DNA strand, it adopts a conformation that is different from both the A and the B forms. The crystal structure of the (PNA) 2 -DNA triplex (10) also showed helical parameters significantly different from those of canonical DNA or RNA helical forms, defining a type of helix, named the P-helix, characterized by a small twist angle, a large x-displacem...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Menchise

Simone

Tedeschi

et al. 2003

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

151

164

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“…33 Previously it had been shown that this tricyclic cytosine analogue discriminates well between G and A targets 34 and also increases the base stacking, thus increasing the melting temperature of DNA-RNA-, 34 DNA-peptide nucleic acid (PNA)-, 35 and PNA-PNA-duplexes 35 . We have shown that, the fluorescence quantum yield of tC is high (20%) and essentially the same whether incorporated into a PNA single strand (22%) or a PNA-DNA-duplex (21%).…”

Section: Introductionmentioning

confidence: 99%

Photophysical Characterization of Fluorescent DNA Base Analogue, tC

et al. 2003

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The neutral, base-pairing form of tC, having a fluorescence quantum yield of 0.2, is found to be the totally predominant species in a wide pH interval, 4-12. We show that the absorption band of tC at lowest energy, centred at 26700 cm -1 and well separated from the nucleobase absorption, is due to a single electronic transition polarized approximately at 35 from the long-axis of the molecule. The 2-deoxyribonucleoside of 1,3-diaza-2-oxophenothiazine, synthesized for further incorporation into DNA was found to display a fluorescence quantum yield nearly the same as in the form of tC that was incorporated into PNA, confirming the notion of the tC nucleoside being a probe with very promising fluorescence properties essentially invariant of environment, also upon incorporation into a DNA strand and upon hybridization.2

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“…(9) [25,26]. The best performance in terms of stabilization of duplexes and triplexes was 7-chloro-1,8-napthyridin-2(1H)-one (7-Cl-bT).…”

Section: Analogs Of Thymine and Cytosinementioning

confidence: 99%

Nucleobase Modifications in Peptide Nucleic Acids

Wojciechowski

Hudson

2007

CTMC

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Peptide nucleic acid (PNA) is an oligonucleotide mimic originally designed upon a repeating N-(2-aminoethyl)glycine polyamide backbone to which nucleobase heterocycles are attached through a methylene carbonyl linkage to the alpha-amino group. These molecules possess remarkable hybridization properties with DNA or RNA forming complexes with high stability and with excellent sequence discrimination despite the substantial structural divergence from natural nucleic acids. Since the disclosure of PNA, a vibrant research community with interest in the chemistry and applications of polyamide-based nucleic acid analogs has developed. This has led to the synthesis and evaluation of a wide variety of modified polyamide nucleic acids. The focus of this report is a comprehensive review of nucleobase modifications in aminoethylglycine (aeg) PNA with reference, where appropriate, to the same modification in DNA or RNA.

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1,8-Naphthyridin-2(1H)-ones − Novel Bicyclic and Tricyclic Analogues of Thymine in Peptide Nucleic Acids (PNAs)

Cited by 61 publications

References 31 publications

Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Photophysical Characterization of Fluorescent DNA Base Analogue, tC

Nucleobase Modifications in Peptide Nucleic Acids

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