7,8-Dihydro-8-oxoadenine as a replacement for cytosine in the third strand of triple helixes. Triplex formation without hypochromicity

Jetter, Michele C.; Hobbs, Frank W.

doi:10.1021/bi00064a006

Cited by 67 publications

(28 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) abolishes the pH sensitivity of the DNA triplex (12,13) without seriously affecting the stability of the triplex. Likewise, 8-oxoadenine has been employed to recognize guanine in the Hoogsteen mode (14)(15)(16)(17). However, synthesis of the PNA pseudoisocytosine monomer seemed more straightforward (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

Egholm¹,

Christensen²,

Dueholm³

et al. 1995

Nucl Acids Res

305

277

View full text Add to dashboard Cite

The synthesis and DNA binding properties of bis-PNA (peptide nucleic acid) are reported. Two PNA segments each of seven nucleobases in length were connected in a continuous synthesis via a flexible linker composed of three 8-amino-3,6-dioxaoctanoic acid units. The sequence of the first strand was TCTCTTT (C-to N-terminal), while the second strand was TTTCTCT or TTTJTJT, where J is pseudoisocytosine. These bisPNAs form triple-stranded complexes of somewhat higher thermal stability than monomeric PNA with complementary oligonucleotides and the thermal melting transition shows very little hysteresis. When the J base is placed in the strand parallel to the DNA complement ('Hoogsteen strand'), the DNA binding was pH independent. The bis-PNAs were also superior to monomeric PNAs for targeting double-stranded DNA by strand invasion.

show abstract

Section: Resultsmentioning

confidence: 99%

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

Egholm¹,

Christensen²,

Dueholm³

et al. 1995

Nucl Acids Res

305

277

View full text Add to dashboard Cite

show abstract

“…The first synthetic purine derivatives to be described were 8-oxoadenine [46,47], Fig. (3b) and its N6-methyl analogue [48], which, in the syn conformation, are arranged so that the 6-amino and N7 protons replace the 4-amino and N3 protons of cytosine.…”

Section: Purine Analoguesmentioning

confidence: 99%

“…In b) -e) the third strand base analogue is shown alone in the same orientation as in a), indicating the substituents that form hydrogen bonds to G. Purine analogues for recognition of GC base pairs in a parallel triplex. a) the parallel G q GC triplet [20,44], b) 8-oxoadenine q GC triplet [46][47][48], c) N 7 -G q GC triplet, d) P1 q GC triplet. donors to interact with O6 and N7.…”

Section: Introductionmentioning

confidence: 99%

Targeting DNA with Triplexes

Fox¹

2000

CMC

192

View full text Add to dashboard Cite

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. In these structures a third strand oligonucleotide binds in the DNA major groove, making specific contacts with substituents on the exposed faces of the base pairs. Although triplexes form with exquisite specificity their use suffers from several drawbacks. Two limitations of this approach, which are considered in this review are, firstly that conditions of low pH are necessary for formation of the C+*GC triplet, and secondly that these structures are often less stable than their duplex counterparts. This review outlines the strategies that have been employed to overcome these drawbacks. The pH problem is addressed by considering the various DNA base analogues that have been used to recognise GC base pairs in a pH independent fashion, and discusses the benefits and limitations of each analogue. Triplex stability can be increased by using novel base analogues, backbone modifications and the use of triplex-specific binding ligands.

show abstract

“…[9,10] Thus, stabilization of the pyrimidine motif triplex at neutral pH is quite necessary for improving the potential of the triplex in various triplex formation-based strategies in vivo. Replacement of the cytosine bases in a homopyrimidine TFO with 5-methylcytosine [7,[11][12][13] or other chemically modified base analogues, [14][15][16][17][18] and conjugation of different DNA intercalators to TFO [19,20] have been used to overcome the requirement of an acidic pH for the pyrimidine motif triplex formation and to stabilize the pyrimidine motif triplex at neutral pH.…”

Section: Introductionmentioning

confidence: 99%

Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition

Torigoe

Rahman

Takuma

et al. 2011

Nucleosides, Nucleotides and Nucleic Acids

View full text Add to dashboard Cite

Due to instability of pyrimidine motif triplex DNA at physiological pH, triplex stabilization at physiological pH is crucial in improving its potential in various triplex formation-based strategies in vivo, such as regulation of gene expression, mapping of genomic DNA, and gene-targeted mutagenesis. To this end, we investigated the effect of our previously reported chemical modification, 2'-O,4'-C-aminomethylene bridged nucleic acid (2',4'- BNA(NC)) modification, introduced into interrupted and continuous positions of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at physiological pH. The interrupted 2',4'-BNA(NC) modifications of TFO increased the binding constant of the triplex formation at physiological pH by more than 10-fold, and significantly increased the nuclease resistance of TFO. On the other hand, the continuous 2',4'-BNA(NC) modification of TFO showed lower ability to promote the triplex formation at physiological pH than the interrupted 2',4'-BNA(NC) modifications of TFO, and did not significantly change the nuclease resistance of TFO. Selection of the interruptedly 2',4'-BNA(NC)-modified positions in TFO was more favorable for achieving the higher binding affinity of the pyrimidine motif triplex formation at physiological pH and the higher nuclease resistance of TFO than that of the continuously 2',4'-BNA(NC)-modified positions in TFO. We conclude that the interrupted 2',4'-BNA(NC) modification of TFO could be a key chemical modification to enhance pyrimidine motif triplex-forming ability and nuclease resistance under physiological condition, and may eventually lead to progress in various triplex formation-based strategies in vivo.

show abstract

7,8-Dihydro-8-oxoadenine as a replacement for cytosine in the third strand of triple helixes. Triplex formation without hypochromicity

Cited by 67 publications

References 42 publications

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA

Targeting DNA with Triplexes

Interrupted 2′-O,4′-C-Aminomethylene Bridged Nucleic Acid Modification Enhances Pyrimidine Motif Triplex-Forming Ability and Nuclease Resistance Under Physiological Condition

Contact Info

Product

Resources

About