scholarly journals NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region

2006 ◽  
Vol 34 (18) ◽  
pp. 5133-5144 ◽  
Author(s):  
Jixun Dai ◽  
Ding Chen ◽  
Roger A. Jones ◽  
Laurence H. Hurley ◽  
Danzhou Yang
Keyword(s):  
Promoter Region ◽  
Solution Structure ◽  
Nmr Solution Structure ◽  
Quadruplex Structure ◽  
G Quadruplex

scholarly journals Effect of Ionic Strength on Porphyrin Drugs Interaction with Quadruplex DNA Formed by the Promoter Region of C-myc and Bcl2 Oncogenes

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Narayana Nagesh ◽  
Varun K. Sharma ◽  
A. Ganesh Kumar ◽  
Edwin A. Lewis
Keyword(s):  
Ionic Strength ◽  
Fluorescence Spectroscopy ◽  
Drug Interactions ◽  
Promoter Region ◽  
Promoter Regions ◽  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Drugs Interaction ◽  
Dna Complex

C-myc and Bcl2 are well characterized oncogenes that are capable of forming G-quadruplex structures. Promoter regions of C-myc and Bcl2 forming G-quadruplex structures are chemically synthesized and G-quadruplex structure is formed in presence of 100 mM potassium ion. Three different porphyrin drugs, namely TMPyP2, TMPyP3, and TMPyP4 are allowed to interact with quadruplex DNA complex and the site and nature of interaction are studied. Drug interactions with quadruplex DNA were carried out in different potassium ionic strengths using fluorescence spectroscopy. It is found that fluorescence hypochromicity decreases with an increase in ionic strength in the case of TMPyP4, TMPyP3, and TMPyP2. Fluorescence titration studies and Job plots indicate that four molecules of TMPyP4, two molecules of TMPyP3 and TMPyP2 are interacting with one molecule of quadruplex DNA.

scholarly journals Use of a Designed Peptide Library to Screen for Binders to a Particular DNA G-Quadruplex Sequence

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Keita Kobayashi ◽  
Noriko Matsui ◽  
Kenji Usui
Keyword(s):  
Clustering Analysis ◽  
Promoter Region ◽  
Peptide Library ◽  
Short Peptides ◽  
Hierarchical Clustering Analysis ◽  
Quadruplex Structure ◽  
Naturally Occurring ◽  
Binding Data ◽  
G Quadruplex ◽  
Screening Guideline

We demonstrated a method to screen for binders to a particular G-quadruplex sequence using easily designed short peptides consisting of naturally occurring amino acids and mining of binding data using statistical methods such as hierarchical clustering analysis (HCA). Despite the small size of the library used in this study, candidates of specific binders were identified. In addition, a selected peptide stabilized the G-quadruplex structure of a DNA oligonucleotide derived from the promoter region of the protooncogene c-MYC. This study illustrates how a peptide library can be designed and presents a screening guideline for construction of G-quadruplex binders. Such G-quadruplex peptide binders could be functionally modified to enable switching, cellular penetration, and organelle-targeting for cell and tissue engineering.

An intramolecular G-quadruplex structure formed in the human MET promoter region and its biological relevance

2015 ◽  
Vol 55 (5) ◽  
pp. 897-909 ◽  
Author(s):  
Jing Yan ◽  
Xiaoyang Zhao ◽  
Bo Liu ◽  
Ying Yuan ◽  
Yifu Guan
Keyword(s):  
Promoter Region ◽  
Quadruplex Structure ◽  
Biological Relevance ◽  
G Quadruplex

scholarly journals Duplex formation in a G-quadruplex bulge

2020 ◽  
Vol 48 (18) ◽  
pp. 10567-10575 ◽  
Author(s):  
Thi Quynh Ngoc Nguyen ◽  
Kah Wai Lim ◽  
Anh Tuân Phan
Keyword(s):  
Base Pair ◽  
Solution Structure ◽  
Biological Significance ◽  
Consensus Definition ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Structural Details ◽  
The Stability ◽  
Definition Of ◽  
Duplex Formation

Abstract Beyond the consensus definition of G-quadruplex-forming motifs with tracts of continuous guanines, G-quadruplexes harboring bulges in the G-tetrad core are prevalent in the human genome. Here, we study the incorporation of a duplex hairpin within a bulge of a G-quadruplex. The NMR solution structure of a G-quadruplex containing a duplex bulge was resolved, revealing the structural details of the junction between the duplex bulge and the G-quadruplex. Unexpectedly, instead of an orthogonal connection the duplex stem was observed to stack below the G-quadruplex forming a unique quadruplex–duplex junction. Breaking up of the immediate base pair step at the junction, coupled with a narrowing of the duplex groove within the context of the bulge, led to a progressive transition between the quadruplex and duplex segments. This study revealed that a duplex bulge can be formed at various positions of a G-quadruplex scaffold. In contrast to a non-structured bulge, the stability of a G-quadruplex slightly increases with an increase in the duplex bulge size. A G-quadruplex structure containing a duplex bulge of up to 33 nt in size was shown to form, which was much larger than the previously reported 7-nt bulge. With G-quadruplexes containing duplex bulges representing new structural motifs with potential biological significance, our findings would broaden the definition of potential G-quadruplex-forming sequences.

scholarly journals Interaction of TMPyP4, TMPyP3, and TMPyP2 with Intramolecular G-Quadruplex Formed by Promoter Region of Bcl2 and KRAS NHPPE

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Narayana Nagesh ◽  
Arumugam Ganesh Kumar
Keyword(s):  
Promoter Region ◽  
Dna Interaction ◽  
Predominant Role ◽  
Promoter Regions ◽  
Ligand Interaction ◽  
Quadruplex Dna ◽  
Molecular Binding ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Structure Environment

Oncogenes are rich in guanine and capable of forming quadruplex structure. Promoter regions oncogenes such as Bcl2 and KRAS NHPPE are rich in guanine content and they can form quadruplex structures. Alterations in the mode and nature of molecular binding to DNA, certainly has effect on the posttranscriptional activities. Recent experiments indicate that structure of quadruplex complex and ligand has predominant role on ligand-quadruplex DNA interaction. In order to understand the nature of each ligand interaction with quadruplex DNA, Bcl2, KRAS NHPPE quadruplex DNA interaction with three porphyrin was studied using spectroscopy, microcalorimetry and mass spectrometry. Our studies, indicate that mode of ligand interaction varies with structure, environment and concentration of ligand. Fluorescence quenching experiments show that TMPyP4 interaction is ligand concentration dependent. Job plots and ITC experiments demonstrate that four molecules of TMPyP4 and two molecules of TMPyP3, TMPyP2 interact with each quadruplex complex. Through ITC titrations, ligand binding constant are higher for TMPyP4 (≈107 M−1) compared to TMPyP3, TMPyP2 (≈105 M−1). ESI-MS experiments confirm the stoichiometry of TMPyP4 : 39Bcl2 is 4 : 1 at saturation and it is 2 : 1 in case of KRAS NHPPE quadruplex.

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