Single Strand Targeted Triplex Formation: Strand Displacement of Duplex DNA by Foldback Triplex-Forming Oligonucleotides

Kandimalla, Ekambar R.; Manning, Adrienne; Agrawal, Sudhir

doi:10.1080/07391102.1995.10508858

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…That is, the 3′-3′ (1) or 5′-5′ (2) oligonucleotide might only be capable of forming a WC base-paired duplex involving its purine domain with the complementary RNA/DNA pyrimidine target strand in 1:1 ratio, while the Hoogsteen pyrimidine domain remains as an overhanging sequence. The sharp, cooperative UV melting profiles (vs broad melting profile for a duplex with a long overhanging Hoogsteen sequence) (Kandimalla & Agrawal, 1994;Kandimalla et al, 1995b), the CD spectral characteristics, and the difference CD spectra do suggest triplex formation.…”

Section: Resultsmentioning

confidence: 94%

Hoogsteen DNA Duplexes of 3‘−3‘- and 5‘−5‘-Linked Oligonucleotides and Triplex Formation with RNA and DNA Pyrimidine Single Strands: Experimental and Molecular Modeling Studies

Kandimalla¹,

Agrawal²

1996

Biochemistry

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DNA oligonucleotide sequences containing two parallel complementary strands attached through 3'-3' and 5'-5' linkages were synthesized. These oligonucleotides from Hoogsteen base-paired parallel-stranded (PS) hairpin duplexes under appropriate conditions [Kandimalla, E. R., Agrawal, S., Venkataraman, G., & Sasisekharan, V. (1995a) J. Am. Chem. Soc. 117, 6416-6417]. UV melting experiments show that these Hoogsteen hairpin duplexes have a lower thermal stability than that of the Watson-Crick (WC) hairpin duplex (antiparallel) of the same sequence. The circular dichroism (CD) spectrum of the Hoogsteen duplex is different from the canonical B-DNA WC duplex spectrum. The formation of the Hoogsteen duplex is pH-dependent since protonation of cytosine requires lower pH conditions. Studies with oligonucleotides of different loop sizes revel that three- and two-base loops are optimum for the formation of stable Hoogsteen duplexes with 3'-3' and 5'-5' linkages, respectively. The guanine residues in the loop stabilize the duplex as a result of G-G interactions as confirmed by molecular modeling studies. The new PS Hoogsteen duplexes form stable triplexes with complementary (antiparallel to the purine domain) single-stranded RNA and DNA pyrimidine sequences in Py.Pu:Py (pyrimidine third strand-purine WC strand:pyrimidine WC strand) motif. The thermal stability of the resulting triplexes is much higher than that of the conventional triplex (binding of a Hoogsteen pyrimidine third strand to a WC duplex) of the same sequence. The CD spectra of the new triplexes are similar to those of conventional triplexes, suggesting that no conformational change occurs as a result of 3'-3' or 5'-5' linkage. A molecular modeling study was carried out to examine the stereochemical feasibility of the Hoogsteen duplexes and formation of triplexes with single-stranded pyrimidine complementary strands.

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Section: Resultsmentioning

confidence: 94%

Hoogsteen DNA Duplexes of 3‘−3‘- and 5‘−5‘-Linked Oligonucleotides and Triplex Formation with RNA and DNA Pyrimidine Single Strands: Experimental and Molecular Modeling Studies

Kandimalla¹,

Agrawal²

1996

Biochemistry

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“…Many studies of triplexes, including NMR and thermodynamic studies, have made use of constructs in which two or all three strands are covalently linked (13,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). However, the relative stability of the Hoogsteen-paired strand is more certain when mixtures are made of separated oligomers.…”

Section: Introductionmentioning

confidence: 99%

Evidence from CD spectra and melting temperatures for stable Hoogsteen-paired oligomer duplexes derived from DNA and hybrid triplexes

Hashem

Wen

et al. 1999

Nucleic Acids Research

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The pyr*pur.pyr type of nucleic acid triplex has a purine strand that is Hoogsteen-paired with a parallel pyrimidine strand (pyr*pur pair) and that is Watson-Crick-paired with an antiparallel pyrimidine strand (pur.pyr pair). In most cases, the Watson-Crick pair is more stable than the Hoogsteen pair, although stable formation of DNA Hoogsteen-paired duplexes has been reported. Using oligomer triplexes of repeating d(AG)12 and d(CT)12 or r(CU)12 sequences that were 24 nt long, we found that hybrid RNA*DNA as well as DNA*DNA Hoogsteen-paired strands of triplexes can be more stable than the Watson-Crick-paired strands at low pH. The structures and relative stabilities of these duplexes and triplexes were evaluated by circular dichroism (CD) spectroscopy and UV absorption melting studies of triplexes as a function of pH. The CD contributions of Hoogsteen-paired RNA*DNA and DNA*DNA duplexes were found to dominate the CD spectra of the corresponding pyr*pur.pyr triplexes.

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“…[46][47][48] Because of the greater complexity of the system, a number of binding modes might be envisioned. 47,49 Examination of models led us to believe that triplex binding domains incorporated into circular oligonucleotides might also interact with duplex DNA in interesting (and potentially useful) ways.…”

Section: Binding Of Duplex Dnamentioning

confidence: 99%

“…Binding of Duplex DNA. More recent studies have described the binding of clamp-type pyrimidine-rich triplex-forming oligonucleotide derivatives or analogues to duplex DNAs. − Because of the greater complexity of the system, a number of binding modes might be envisioned. , Examination of models led us to believe that triplex binding domains incorporated into circular oligonucleotides might also interact with duplex DNA in interesting (and potentially useful) ways. Thus in 1993 we turned our attention to whether triplex-forming circular structures such as 1 or 24 could bind to a complementary target in duplex DNA and, if so, by what mode of binding. , …”

Section: Recognition Of Nucleic Acidsmentioning

confidence: 99%

“…More recent studies have described the binding of clamp-type pyrimidine-rich triplex-forming oligonucleotide derivatives or analogues to duplex DNAs. [46][47][48] Because of the greater complexity of the system, a number of binding modes might be envisioned. 47,49 Examination of models led us to believe that triplex binding domains incorporated into circular oligonucleotides might also interact with duplex DNA in interesting (and potentially useful) ways.…”

Section: Recognition Of Nucleic Acidsmentioning

confidence: 99%

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Recognition of DNA, RNA, and Proteins by Circular Oligonucleotides

Kool

1998

Acc. Chem. Res.

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IntroductionWhile the backbone organization of DNA and RNA is normally quite regular, there are many structural forms which these molecules can adapt by undergoing various secondary and tertiary helical and folded interactions, by being subjected to twisting and bending, and by interconversion between various topological and knotted variations. Probably the most common structural form of DNA in nature is a long double helix in which the ends are joined into a circle. The genomes of most lower organisms are organized in this way, 1 and clearly this circular structure lends some important advantage to these organisms or evolution would not have selected for it.Most chemists are chiefly interested in structure and reactivity of molecules smaller than entire bacterial genomes; such large circular DNAs will not be discussed herein for that reason. Of particular interest, then, is the question: what are the smallest cyclic DNAs or RNAs which exist in nature? For DNA, the answer appears to be several hundred to perhaps 1500 nucleotides (nt), which is still rather large. For RNA, probably the smallest known circular structures are the viroid RNAs, which are single-stranded and as small as 246 nucleotides in size. 2 However, this is far from the smallest possible cyclic nucleic acid structure. Duplex DNA can exist in circles at least as small as 125 bp (base pairs); 3 cyclic structures smaller than this are difficult to achieve because of the rigidity of the double helix. 4 Single-stranded DNA and RNAs do not have this problem, and rings as small as two nucleotides are known. 5 Thus, the realm of possible cyclic DNA and RNA structures falls easily into the size range most palatable to chemists.Interestingly, although small synthetic circular DNAs had been reported a number of times as early as in 1968, 6 prior to 1990 there were no reported studies investigating the effect of this quite significant structural modification on DNA's molecular recognition properties. Despite this, there was quite reasonable precedent that such a structural alteration might have a large effect on such recognition properties. Indeed, in recent decades it has become widely recognized that macrocyclic molecular structures can have strong advantages in the formation of noncovalent complexes. 7 Among these advantages (relative to noncyclic molecules of similar structure) are tighter binding affinity and greater specificity for binding the target of interest. The advent of simple synthetic approaches to the construction of oligonucleotides has led to an explosion of studies aimed at studying and modifying their noncovalent binding properties. In our early work we proposed that the principle of macrocyclic recognition could also be applied to nucleic acids in small synthetic well-defined systems. The testing of that hypothesis is the subject of this Account. Recognition of Nucleic AcidsIn 1990 when we began our studies it was not trivial to synthesize a circular oligonucleotide from a linear precursor; however, the development of new synthetic meth...

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Single Strand Targeted Triplex Formation: Strand Displacement of Duplex DNA by Foldback Triplex-Forming Oligonucleotides

Cited by 7 publications

References 25 publications

Hoogsteen DNA Duplexes of 3‘−3‘- and 5‘−5‘-Linked Oligonucleotides and Triplex Formation with RNA and DNA Pyrimidine Single Strands: Experimental and Molecular Modeling Studies

Hoogsteen DNA Duplexes of 3‘−3‘- and 5‘−5‘-Linked Oligonucleotides and Triplex Formation with RNA and DNA Pyrimidine Single Strands: Experimental and Molecular Modeling Studies

Evidence from CD spectra and melting temperatures for stable Hoogsteen-paired oligomer duplexes derived from DNA and hybrid triplexes

Recognition of DNA, RNA, and Proteins by Circular Oligonucleotides

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