Reconciliation of the X-ray and NMR Structures of the Thrombin-Binding Aptamer d(GGTTGGTGTGGTTGG)

Kelly, Jennifer A.; Feigon, Juli; Yeates, Todd O.

doi:10.1006/jmbi.1996.0097

Cited by 191 publications

(171 citation statements)

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“…This is not true for the unmodified TBA with alternating syn and anti deoxyguanosines in every GG pair. 5 Similar to the natural prototype, GQs modified in the loop region did not show any signs of hysteresis in heating-cooling cycles at the temperature ramp rate of 0.2 °C/min. Slow or fast annealing of the samples before melting also did not affect the observed denaturation profiles.…”

Section: Thermal Stability Of the Chimeric Tbasmentioning

confidence: 57%

“…Based on an NMR model of TBA, these bases are stacked with the neighboring G-quartet in an unmodified aptamer and hydrogen bonded to each other. 5 Other NMR and crystallographic studies of TBA highlighted an important role of T4-T13 base pair stacking on the stabilization of GQ structure. 8,35 Modifications of the TT loops that favor the optimal pairing of stacked thymines may considerably increase the thermal stability of non-natural TBA.…”

Section: Discussionmentioning

confidence: 99%

“…It forms intramolecular GQ with two G-quartets in the core and three loops, one TGT and two TT loops. 5,6 It has been established that aptamer loops are involved in recognition of the fibrinogen-binding site of the protein (exosite I) in a TBA-thrombin complex. 7 The most recent model for the aptamer binding motif suggests that the TT loops act as a pincer-like system that embraces the protruding region of thrombin exosite I while the TGT loop is being fully exposed to the solvent.…”

Section: Introductionmentioning

confidence: 99%

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Anomeric DNA quadruplexes

Kolganova

Varizhuk

Новиков

et al. 2014

Artificial DNA: PNA & XNA

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Section: Thermal Stability Of the Chimeric Tbasmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anomeric DNA quadruplexes

Kolganova

Varizhuk

Новиков

et al. 2014

Artificial DNA: PNA & XNA

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“…This holds true for the most studied of aptamer protein complexes. The thrombin aptamer binds primarily by electrostatic binding at a surface fold that contains many exposed arginine and lysine residues [55,56]. The change in conformation associated with aptamer recognition stands in contrast to the entropically-driven minor groove binding of many hydrophobic drugs to dsDNA.…”

Section: Thermodynamics Of Rna and Dna Aptamer Bindingmentioning

confidence: 99%

Thermodynamics of Nucleic Acid Structural Modifications for Biotechnology Applications

Franzen¹

2011

Biotechnology of Biopolymers

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IntroductionThe repertoire of chemistry available to native nucleotides in DNA and RNA is limited to the purine and pyrimidine functional groups, along with the special role of the 2'-hydroxyl of RNA. The nucleobases have exocyclic amino groups and imines, neither of which is highly reactive or a good candidate for catalytic function. One might argue that the limited range of chemical reactivity is an evolutionary advantage in molecules whose functions are primarily to store (DNA) and process (RNA) genetic information. The most important attribute of both DNA and RNA is the molecular recognition through base pairing. The hydrogen bond pattern combined with the conformation of the ribose sugar gives rise to the specific B-form double helix in DNA and A-form helix with a range of additional standard folds in RNA, loops, bulges and pseudoknots. These structures are well known for their ability to interact with proteins to provide a scaffold for transcription (DNA → RNA) to create messenger RNA (mRNA), and processing of mRNA by enzymes that have active components composed of RNA molecules. The chemical action of RNA on other RNAs by means of the 2'-hydroxyl is an exception to the lack or reactivity of DNA and RNA. Selfsplicing by action of the 2'-hydroxyl as a nucleophile was the process that broke the dogma that RNA is always a passive molecule that simply transmits information [1]. Indeed, RNA i s v e r y a c t i v e i n p r o c e s s i n g o t h e r R N A s u s i n g t h e 2 ' -h y d r o x y l a s a n u c l e o p h i l e f o r hydrolysis of the phosphodiester bond leading to cleavage or to rearrangements of structure such as RNA splicing. Outside of this reactivity, the components of the purine and pyrimidine rings are largely inert. Aromatic amines are poor nucleophiles, and imines are even less reactive. The purine and pyrimidine rings are not particularly electrophilic because of the nitrogen heteroatoms and carbonyls. Using in vitro selection (also known as SELEX) [2][3][4], and appropriate modification, RNA and DNA have been developed for numerous applications that transcend their biological functions. In this chapter we will consider the modifications of the nucleobase as a means to expand upon the native function. The extensive literature on modifications of the phosphodiester backbone and the ribose sugar will not be considered in this chapter due to space limitations. Base modifications may consist of expansions of the purine/pyrimidine ring, appended functional group or chemical modification to increase the stability of the backbone with respect to hydrolysis. Expanded DNA or xDNA has been developed as mimics of native DNA with potential biotechnology applications [5,6]. In these molecules, the purine and pyrimidine rings are fused to phenyl or naphthyl rings to give rise to

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“…This intramolecular triplex was obtained by folding back twice on itself of the 5′-CTC CTC CCT CCT -L-AGG AGG GAG GAG -L-GTG GTG GGT GGT-3′ oligonucleotide, where -L-is the hydroxyalkyl linker pO(CH 2 CH 2 O) 3 p. The use of such a molecule had been *To whom correspondence should be addressed. Tel: +33 1 4838 7690; Fax: +33 1 4837 7443; Email: eliane.taillandier@smbh.univ-paris13.fr adopted because it: (i) avoids strand stoicheiometry problems; (ii) allows the unambiguous definition of the third strand orientation; (iii) increases the stability of the triplex when compared to a triplex formed by separate strands with identical sequences; and (iv) reduces the possibility of the formation of intermolecular structures by GT-rich oligonucleotides such as tetraplexes (22)(23)(24) or aptamers (25)(26)(27)(28). The present investigation is aimed at studying the formation of the intramolecular triple helix involving the same strands but with a parallel third strand orientation.…”

Section: Introductionmentioning

confidence: 99%