Sequence specificity of the non-natural pyrido[2,3-<i>d</i>]pyrimidine nucleoside in triple helix formation

Staubli, Andrea B.; Dervan, Peter B.

doi:10.1093/nar/22.13.2637

Cited by 16 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The T.AT triplet is less stable than C + .GC [6][7][8][9] and requires millimolar concentrations of magnesium for effective formation [4]. Several strategies have been employed to enhance the stability of this triplet, including increasing the aromatic surface area [10] and altering the backbone conformation to N3 -P5 [11], PNA (peptide nucleic acid) [12,13] or LNA (locked nucleic acid) [14,15] (third strands with N-type sugar conformations are more stable than S-type and RNA-like third strands bind well to duplex DNA targets [16,17]). We have sought to increase stability by the addition of positively charged groups to the sugar, the base or both.…”

Section: Increasing Affinitymentioning

confidence: 99%

Formation of stable DNA triplexes

Fox

Brown

2011

Biochemical Society Transactions

View full text Add to dashboard Cite

Triple-helical nucleic acids are formed by binding an oligonucleotide within the major groove of duplex DNA. These complexes offer the possibility of designing oligonucleotides which bind to duplex DNA with considerable sequence specificity. However, triple-helix formation with natural nucleotides is limited by (i) the requirement for low pH, (ii) the requirement for homopurine target sequences, and (iii) their relatively low affinity. We have prepared modified oligonucleotides to overcome these limitations, including the addition of positive charges to the sugar and/or base, the inclusion of cytosine analogues, the development of nucleosides for recognition of pyrimidine interruptions and the attachment of one or more cross-linking groups. By these means we are able to generate triplexes which have high affinities at physiological pH at sequences that contain pyrimidine interruptions.

show abstract

Section: Increasing Affinitymentioning

confidence: 99%

Formation of stable DNA triplexes

Fox

Brown

2011

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…One of the first such analogues to be tested was a pyrido[2,3-d]pyrimidine derivative (F) [76]. This base selectively recognises AT base pairs, forming the F q AT triplet, utilising the tautomer shown in Fig.…”

Section: Improved Base Stackingmentioning

confidence: 99%

“…Thirdly triplex stability may be enhanced by increasing the base stacking in the third strand. However, simple addition of aromatic rings to the pyrimidine nucleus does not seem to be of benefit [76][77][78][79], possibly because the improved stacking of the single stranded oligonucleotide hinders triplex formation. Other stacking interactions, such as those involving appended propynyl or propargylamino groups [72][73][74][75], may be a better option.…”

Section: Future Prospectsmentioning

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

“…An alternative less selective approach has been to use base analogues or linkers that skip or intercalate at such inversions (36–38). Attempts to increase the strength of binding of TFOs have included the addition of positively charged groups (39–42), increasing the base stacking (43,44) or changing the phosphodiester backbone (2). …”

Section: Introductionmentioning

confidence: 99%

Four base recognition by triplex-forming oligonucleotides at physiological pH

Rusling

Powers²,

Ranasinghe³

et al. 2005

Nucleic Acids Research

133

View full text Add to dashboard Cite

We have achieved recognition of all 4 bp by triple helix formation at physiological pH, using triplex-forming oligonucleotides that contain four different synthetic nucleotides. BAU [2′-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine] recognizes AT base pairs with high affinity, MeP (3-methyl-2 aminopyridine) binds to GC at higher pHs than cytosine, while APP (6-(3-aminopropyl)-7-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one) and S [N-(4-(3-acetamidophenyl)thiazol-2-yl-acetamide)] bind to CG and TA base pairs, respectively. Fluorescence melting and DNase I footprinting demonstrate successful triplex formation at a 19mer oligopurine sequence that contains two CG and two TA interruptions. The complexes are pH dependent, but are still stable at pH 7.0. BAU, MeP and APP retain considerable selectivity, and single base pair changes opposite these residues cause a large reduction in affinity. In contrast, S is less selective and tolerates CG pairs as well as TA.

show abstract

Sequence specificity of the non-natural pyrido[2,3-d]pyrimidine nucleoside in triple helix formation

Abstract: The non-natural pyrido [2,3-d]

Cited by 16 publications

References 31 publications

Formation of stable DNA triplexes

Formation of stable DNA triplexes

Targeting DNA with Triplexes

Four base recognition by triplex-forming oligonucleotides at physiological pH

Contact Info

Product

Resources

About