Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Constant, Jean‐François; Laugâa, Philippe; Roques, Bernárd P.; Lhomme, Jean

doi:10.1021/bi00411a016

Cited by 32 publications

(23 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the two edges of the triazine heterocycle have the potential to form simultaneously a full set of hydrogen bonds with the poorly paired thymine or uracil bases. By analogy with nucleobase-acridine conjugates (14), stacking of the triaminotriazine and acridine units should decrease nonspecific, intercalative binding to duplex DNA and RNA. Although 9-aminoacridine derivatives bind in the minor groove, molecular modeling using MOE suggested that ligand 1 could target CTG and CUG through either minor or major grooves as a ''stacked intercalator.''…”

Section: Resultsmentioning

confidence: 99%

A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding

Arambula

Ramisetty

Baranger

et al. 2009

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

207

246

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding

Arambula

Ramisetty

Baranger

et al. 2009

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

207

246

View full text Add to dashboard Cite

show abstract

“…Thermodynamic signatures for self-association of purine and pyrimidine derivatives in aqueous solution (enthalpically favorable but entropically unfavorable) have been interpreted to imply that these associations are driven by intrinsic attractions between the heterocyclic rings, rather than by their mutual exclusion from water. The nature of the attraction between the heterocycles is uncertain; both dispersion forces and interactions between partial charges within the adjacent rings have been assumed (36,37). In a recent study, involving naphthyl and adenine moieties connected through a carboxylated propylene linker, Newcomb and Gellman (26) suggested that attractive interactions between partial positive and negative charges along with a "nonclassical" hydrophobic effect may be the main driving forces for stacking in aqueous solutions.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of Stacked and Quenched Uridine Nucleotide Fluorophores

Dhar

Bhaduri

1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Since the seminal work of Weber and Laurence (1) with 1-anilinonaphthalene-8-sulfonic acid, extrinsic fluorescent probes have been extensively used to monitor various aspects of protein-ligand or enzyme-substrate interactions. Among others, these probes have been used (i) to establish the degree of polarity or hydrophobicity of a particular region of a protein, (ii) to measure the distance between groups on protein surface, (iii) to measure the extent of flexibility of protein in solution, (iv) to measure the rate of very rapid conformational transitions, and (v) to measure kinetic constants of interaction between protein and ligand (2). To facilitate these studies, a variety of derivatized fluorescent ligands or substrate analogs have been synthesized over the years without any serious attention being given to their solution conformations or their transitions to new conformations on interaction with the target proteins. Such conformational transitions are often crucial steps in biological interactions as typically exemplified by NAD, the common cofactor for a very large number of dehydrogenases. The molecule exhibits reversible stacking between the adenine and pyridine moiety with both the open and the closed forms in rapid interconversionary equilibrium in aqueous solutions (3, 4). During catalysis, NAD takes a totally extended conformation on the enzyme surface; the conserved tertiary structure of the pyridine nucleotide binding site being a very characteristic feature of all these oxidoreductases (5).Etheno-ATP was originally synthesized as a fluorescent analog of ATP. It had a high quantum yield and a long fluorescence lifetime and could be used to follow ATP interactions primarily by polarization studies (6 -8). In contrast, as in case of NAD, significant population of etheno-NAD was in a folded conformation in aqueous solution as a result of aromatic interactions between the pyridine and the modified adenine moiety, leading to dynamic collisional quenching of fluorescence and short fluorescence life-time (9). This stacked and quenched fluorophore was brilliantly used to establish negative co-operativity for glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle for the binding of the tetrameric apoenzyme to the coenzyme. The conformational transition of etheno-NAD from folded to stretched conformation as reflected by its enhanced fluorescence on interaction with the target protein was the monitoring parameter for this purpose (10). Although stacked fluorophore with quenched fluorescence can be of immense use in protein-ligand binding studies, as is exemplified by etheno-NAD, it is surprising to note that no deliberate effort has so far been made to design such compounds taking advantage of the potential aromatic interaction between the attached fluorophore and a suitable moiety of the desired biomolecule.The interaction between aromatic rings is of wide chemical and biological interest, because it plays important roles in vital biological processes, such as stabilization of protein and nucleic acid s...

show abstract

“…Particularly striking is the characteristic diminution of the intensity of absorption near 260 nm (the so-called hypochromic effect), well documented experimentally and understood theoretically (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 88%

Self-association of caffeine in aqueous solution: an FT-IR study

Falk¹,

Gil²,

Iza³

1990

Can. J. Chem.

View full text Add to dashboard Cite

MICHAEL FALK, MANUEL GIL, and NEREA IZA. Can. J. Chem. 68, 1293 (1990). Spectra of caffeine in DzO solution (0.003 to 0.129 M) were studied by Fourier-transform infrared spectroscopy. Spectral changes in the carbonyl stretching region were interpreted in terms of the self-association equilibria resulting from the stacking of caffeine molecules. Absence of isosbestic points indicated the occurrence of more than two spectroscopically distinct caffeine species. A simple monomer-dimer-polymer model was employed, in which the successive equilibria are governed by two association constants, Kd for the formation of dimers and K, for the formation of trimers and larger polymers. The value Kd = 158.1 L mol-I was taken from a recent ultraviolet study by Iza et al. and the value K, = 27 L mol-' was derived from the analysis of infrared band profiles sharpened by Fourier self-deconvolution. From these values of Kd and K,, the weight fractions of monomers, dimers, and polymers were calculated for every caffeine concentration and their individual molar absorptivity spectra were derived. In agreement with the earlier work of Maevsky and Sukhorukov, it was found that stacking association causes shifts of both C=O stretching fundamentals to higher wavenumbers. The monomer-dimer shifts are smaller than the dimerpolymer shifts. Analogous shifts were observed for the stacking self-association of 1,3-dimethyluracil in D 2 0 . The shifts to higher wavenumbers are probably caused by the diminished hydrogen bonding of water to C=O groups of the stacked bases.Key words: caffeine, self association, infrared spectroscopy, base stacking.MICHAEL FALK, MANUEL GIL et NEREA IZA. Can. J. Chem. 68, 1293 (1990). Nous avons CtudiC les spectres de la cafkine dans des solutions de D 2 0 (0.003 ? I 0.129 M) par la spectroscopie infrarouge 5 transformke de Fourier. La variation des spectres dans la region de vibration de valence des groupes C=O a Ctk interpret6 en termes des Cquilibres impliquant l'auto-association par empilage de molkcules de cafkine. L'absence de points isosbestiques a indiquC l'existence d'au moins trois espkces distinctes de cafkine. Nous avons employ6 un modkle monomkre-dimkrepolymkre, dans lequel les Cquilibres successifs sont controlks par deux constantes d'association, Kd pour la dimkrization et K , pour la formation de trimkres et de polymkres plus grands. La valeur Kd = 158.1 L mol-I a CtC prise de 1'Ctude rCcente faite par Iza et al., tandis que la valeur K, = 27 L mol-' a CtC derivke de l'analyse des profiles de bandes infrarouges obtenues par auto-dCconvolution. A partir des valeurs de Kd et K,, nous avons calculk la fraction en poids des monomkres, dimkres et polymkres pour chaque concentration de cafCine, ce qui nous a permis de calculer leurs spectres individuels. En accord avec les travaux antCrieurs de Maevsky et Sukhorukov, nous avons trouvC que l'association par empilage cause des dCplacements de vibrations de valence des groupes C=O vers les hautes frkquences. Les dkplacements monomkre-dimkre sont moins grands que...

show abstract

Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and interactions with DNA

Cited by 32 publications

References 33 publications

A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding

A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding

Synthesis and Characterization of Stacked and Quenched Uridine Nucleotide Fluorophores

Self-association of caffeine in aqueous solution: an FT-IR study

Contact Info

Product

Resources

About