Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA‐1 erythroid transcription factor

Foti, Matthew; Omichinski, James G.; Stahl, Stephen J.; Maloney, Donna; West, John A.; Schweitzer, Barry

doi:10.1016/s0014-5793(99)00026-5

Cited by 3 publications

(3 citation statements)

References 46 publications

(61 reference statements)

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“…For example, AraC substitution into the recognition site for the GATA-1 erythroid transcription factor did not affect the affinity of a DNA duplex for the cognate DNA binding domain. 41 In contrast, the antiviral agent ganciclovir did reduce protein binding by a factor of 10 in this system. These researchers had previously investigated the effect of AraC substitution in duplex DNA and also identified localized structural perturbations due to AraC substitution.…”

Section: 22mentioning

confidence: 70%

Antimetabolite incorporation into DNA: Structural and thermodynamic basis for anticancer activity

Gmeiner

2002

Biopolymers

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Antimetabolites are a class of effective anticancer drugs that structurally resemble naturally occurring biochemicals and interfere in essential biochemical processes. In this review, the recent literature describing investigations of the structural and thermodynamic basis for the anticancer activity of three antipyrimidines [1-beta-D-arabinofuranosyl cytidine (AraC). 2',2'-difluoro deoxycytidine (dFdC), and 5-fluoro-2'-deoxyuridine (FdUrd)] is summarized. Our laboratory, and others, have shown that misincorporation of any of these three antipyrimidines into DNA perturbs the structure and decreases the stability of duplex DNA. These data are useful for rationalizing the effects of antipyrimidine misincorporation on the activities of proteins required for DNA replication and repair such as DNA topoisomerase 1 and DNA polymerases. The studies completed to date and summarized in this review demonstrate the utility of investigations into the structure-function relationships between antipyrimidine-substituted DNA complexed with DNA-modifying proteins for the purpose of understanding the basis for effective antipyrimidine cancer chemotherapy and the future design of novel anticancer drugs.

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Section: 22mentioning

confidence: 70%

Antimetabolite incorporation into DNA: Structural and thermodynamic basis for anticancer activity

Gmeiner

2002

Biopolymers

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“…The weaknesses of aptamer beacons appeared to be: 1) the potential failure of some candidate beacons to open their stem region and allow the dequenching or fluorescence emission of F upon analyte binding, 2) difficulty in identifying secondary loop structures that could be used as potential beacons especially if ligandinduced fit in a duplex or double-stranded (ds) stem region was the mode of aptamer binding. The weaknesses of signaling aptamers appeared to be: 1) the relatively weak quenching ability of NTPs [1,3,5], thereby leading to potentially higher background fluorescence and reduced assay sensitivity, 2) relatively complicated multi-step methods for identifying naturally selected signaling aptamers or engineering signaling aptamers based on large bodies of data to place F in the binding region of an aptamer structure such that F would not affect aptamer binding to the target ligand [27].…”

Section: Introductionmentioning

confidence: 99%

“…We were also conscious of the need to place F and Q in such a way that they did not affect the binding affinity or specificity of the aptamer [27]. This can be quite problematic even when one knows the aptamer binding site or pocket and subsequently attempts to engineer the placement of F and Q.…”

Section: Introductionmentioning

confidence: 99%

Development of Naturally Selected and Molecularly Engineered Intrachain and Competitive FRET-Aptamers and Aptamer Beacons

Bruno

Zúñiga²,

Carrillo³

et al. 2011

CCHTS

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Several different approaches have been taken to development of homogeneous fluorescent aptamer assays including end-labeled beacons and signaling aptamers which are intrinsically quenched by nucleotides. Two new strategies dubbed "intrachain" and "competitive" FRET-aptamer assays are summarized in this review. Intrachain and competitive FRET-aptamers can be engineered on the molecular level through a series exploratory experiments involving prior knowledge of aptamer secondary or tertiary structures and hypotheses about aptamer conformational changes. However, there is an intrinsic risk of altering aptamer affinity or specificity associated with chemical modifications of an aptamer. Natural selection methods for FRET-aptamers have also been devised to potentially obviate the chemical modification problem. The naturally selected aptamers are subjected to fluorophore (F)- and or quencher (Q)-conjugated nucleotide triphosphate (NTP) incorporation by polymerase chain reaction (PCR) with permissive polymerases such as Deep Vent exo-, but still demonstrate sensitive and specific assay performance despite modified bases, because they are ultimately selected after decoration with F and Q. This paper summarizes work in this area and presents some new examples of the engineered and naturally selected FRET-aptamers for detection of vitamin D.

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A Knowledge-Based Energy Function for Protein−Ligand, Protein−Protein, and Protein−DNA Complexes

et al. 2005

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We developed a knowledge-based statistical energy function for protein-ligand, protein-protein, and protein-DNA complexes by using 19 atom types and a distance-scale finite ideal-gas reference (DFIRE) state. The correlation coefficients between experimentally measured protein-ligand binding affinities and those predicted by the DFIRE energy function are around 0.63 for one training set and two testing sets. The energy function also makes highly accurate predictions of binding affinities of protein-protein and protein-DNA complexes. Correlation coefficients between theoretical and experimental results are 0.73 for 82 protein-protein (peptide) complexes and 0.83 for 45 protein-DNA complexes, despite the fact that the structures of protein-protein (peptide) and protein-DNA complexes were not used in training the energy function. The results of the DFIRE energy function on protein-ligand complexes are compared to the published results of 12 other scoring functions generated from either physical-based, knowledge-based, or empirical methods. They include AutoDock, X-Score, DrugScore, four scoring functions in Cerius 2 (LigScore, PLP, PMF, and LUDI), four scoring functions in SYBYL (F-Score, G-Score, D-Score, and ChemScore), and BLEEP. While the DFIRE energy function is only moderately successful in ranking native or near native conformations, it yields the strongest correlation between theoretical and experimental binding affinities of the testing sets and between rmsd values and energy scores of docking decoys in a benchmark of 100 protein-ligand complexes. The parameters and the program of the all-atom DFIRE energy function are freely available for academic users at http://theory.med.buffalo.edu.

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Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA‐1 erythroid transcription factor

Cited by 3 publications

References 46 publications

Antimetabolite incorporation into DNA: Structural and thermodynamic basis for anticancer activity

Antimetabolite incorporation into DNA: Structural and thermodynamic basis for anticancer activity

Development of Naturally Selected and Molecularly Engineered Intrachain and Competitive FRET-Aptamers and Aptamer Beacons

A Knowledge-Based Energy Function for Protein−Ligand, Protein−Protein, and Protein−DNA Complexes

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