Selectivity of small molecule ligands for parallel and anti-parallel DNA G-quadruplex structures

2009 ◽  
Vol 7 (20) ◽  
pp. 4194 ◽  
Author(s):  
Thomas P. Garner ◽  
Huw E. L. Williams ◽  
Katarzyna I. Gluszyk ◽  
Stephen Roe ◽  
Neil J. Oldham ◽  
...  
Keyword(s):  
Small Molecule ◽  
G Quadruplex ◽  
Small Molecule Ligands

Benzothiazole hydrazones of furylbenzamides preferentially stabilize c-MYC and c-KIT1 promoter G-quadruplex DNAs

2016 ◽  
Vol 14 (24) ◽  
pp. 5779-5793 ◽  
Author(s):  
Sushree Prangya Priyadarshinee Pany ◽  
Praneeth Bommisetti ◽  
K. V. Diveshkumar ◽  
P. I. Pradeepkumar
Keyword(s):  
Small Molecule ◽  
Anticancer Agents ◽  
Next Generation ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
Small Molecule Ligands

The stabilization of G-quadruplex DNA structures by using small molecule ligands having simple structural scaffolds has the potential to be harnessed for developing next generation anticancer agents.

Synthetic Small Molecules Targeting G-Quadruplexes and their Application

2015 ◽  
Vol 1088 ◽  
pp. 507-513
Author(s):  
Hui Yu ◽  
Yan Li Wang ◽  
Xiao Yin Zhao ◽  
Wen Zhang
Keyword(s):  
Drug Design ◽  
Small Molecules ◽  
Small Molecule ◽  
Binding Mode ◽  
Current Understanding ◽  
Promising Target ◽  
G Quadruplex ◽  
Small Molecule Ligands

G-quadruplex is expected to be a promising target for drug design. The manually synthesized small-molecule compounds are able to induce the formation of and stabilize G-quadruplexes. In this paper, we summarize the current understanding of the structure of G-quadruplexes, the binding mode of G-quadruplexes and small-molecule ligands, and important synthesized small molecules targeting G-quadruplexes as potential drugs.

scholarly journals Small Molecule Fluorescent Probes for G- Quadruplex Visualization as Potential Cancer Theranostic Agents

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 752 ◽  
Author(s):  
Pallavi Chilka ◽  
Nakshi Desai ◽  
Bhaskar Datta
Keyword(s):  
Small Molecule ◽  
Fluorescent Probes ◽  
Cancer Prognosis ◽  
Fluorescence Signal ◽  
Physiological Relevance ◽  
G Quadruplex ◽  
Small Molecule Ligands ◽  
Recent Developments ◽  
Theranostic Agents

G-quadruplexes have gained prominence over the past two decades for their role in gene regulation, control of anti-tumour activity and ageing. The physiological relevance and significance of these non-canonical structures in the context of cancer has been reviewed several times. Putative roles of G-quadruplexes in cancer prognosis and pathogenesis have spurred the search for small molecule ligands that are capable of binding and modulating the effect of such structures. On a related theme, small molecule fluorescent probes have emerged that are capable of selective recognition of G-quadruplex structures. These have opened up the possibility of direct visualization and tracking of such structures. In this review we outline recent developments on G-quadruplex specific small molecule fluorescent probes for visualizing G-quadruplexes. The molecules represent a variety of structural scaffolds, mechanism of quadruplex-recognition and fluorescence signal transduction. Quadruplex selectivity and in vivo imaging potential of these molecules places them uniquely as quadruplex-theranostic agents in the predominantly cancer therapeutic context of quadruplex-selective ligands.

scholarly journals Quantifying the impact of small molecule ligands on G-quadruplex stability against Bloom helicase

2019 ◽  
Vol 47 (20) ◽  
pp. 10744-10753 ◽  
Author(s):  
Parastoo Maleki ◽  
Golam Mustafa ◽  
Prabesh Gyawali ◽  
Jagat B Budhathoki ◽  
Yue Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thermal Stability ◽  
Small Molecule ◽  
Single Molecule ◽  
Telomerase Activity ◽  
G Quadruplex ◽  
Small Molecule Ligands ◽  
The Impact ◽  
Different Levels ◽  
Thermal Stability Of

Abstract G-quadruplex (GQ) stabilizing small molecule (SM) ligands have been used to stabilize human telomeric GQ (hGQ) to inhibit telomerase activity, or non-telomeric GQs to manipulate gene expression at transcription or translation level. GQs are known to inhibit DNA replication unless destabilized by helicases, such as Bloom helicase (BLM). Even though the impact of SM ligands on thermal stability of GQs is commonly used to characterize their efficacy, how these ligands influence helicase-mediated GQ unfolding is not well understood. Three prominent SM ligands (an oxazole telomestatin derivative, pyridostatin, and PhenDC3), which thermally stabilize hGQ at different levels, were utilized in this study. How these ligands influence BLM-mediated hGQ unfolding was investigated using two independent single-molecule approaches. While the frequency of dynamic hGQ unfolding events was used as the metric in the first approach, the second approach was based on quantifying the cumulative unfolding activity as a function of time. All three SM ligands inhibited BLM activity at similar levels, 2–3 fold, in both approaches. Our observations suggest that the impact of SM ligands on GQ thermal stability is not an ideal predictor for their inhibition of helicase-mediated unfolding, which is physiologically more relevant.

scholarly journals Allergens and their associated small molecule ligands ‐ their dual role in sensitization

Allergy ◽  
2021 ◽  
Author(s):  
Maksymilian Chruszcz ◽  
Fook Tim Chew ◽  
Karin Hoffmann‐Sommergruber ◽  
Barry K. Hurlburt ◽  
Geoffrey A. Mueller ◽  
...  
Keyword(s):  
Small Molecule ◽  
Dual Role ◽  
Small Molecule Ligands

Research Progress in the Typical Structure of Human Telomeric G-Quadruplex

2014 ◽  
Vol 955-959 ◽  
pp. 419-422
Author(s):  
Gui Lin Liu ◽  
Yan Ping Ding ◽  
Yan Ling Wu ◽  
Wen Zhang
Keyword(s):  
Cell Cycle ◽  
Dna Sequences ◽  
Research Progress ◽  
Human Chromosomes ◽  
Telomeric Dna ◽  
Typical Structure ◽  
Special Sequence ◽  
Physiological Processes ◽  
G Quadruplex ◽  
Small Molecule Ligands

Telomeric DNA of human chromosomes plays a significant role in physiological processes such as cell cycle, aging, cancer and genetic stability due to its special sequence and structure. The research on small molecule ligands targeting G-quadruplex formed by such special sequence has attracted considerable attention, and has achieved great breakthrough. In this paper, we summarize the DNA sequences and structures of three kinds of typical human telomeric G-quadruplex, providing an important reference for further research.

Targeting FKBP isoforms with small-molecule ligands

2011 ◽  
Vol 11 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Elizabeth A Blackburn ◽  
Malcolm D Walkinshaw
Keyword(s):  
Small Molecule ◽  
Small Molecule Ligands

scholarly journals Actions of the Small Molecule Ligands SW106 and AH-3960 on the Type-1 Parathyroid Hormone Receptor

2015 ◽  
Vol 29 (2) ◽  
pp. 307-321 ◽  
Author(s):  
Percy H. Carter ◽  
Thomas Dean ◽  
Brijesh Bhayana ◽  
Ashok Khatri ◽  
Raj Rajur ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Small Molecule ◽  
Hormone Receptor ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Blood Calcium ◽  
Parathyroid Hormone Receptor ◽  
Peptide Analog ◽  
Amino Terminal ◽  
Small Molecule Ligands

Abstract The parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating blood calcium levels and bone metabolism and is thus of interest for small-molecule ligand development. Of the few small-molecule ligands reported for the PTHR1, most are of low affinity, and none has a well-defined mechanism of action. Here, we show that SW106 and AH-3960, compounds previously identified to act as an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT, a PTHR1 construct that lacks the large amino-terminal extracellular domain used for binding endogenous PTH peptide ligands, with the same micromolar affinity with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP signaling induced by the peptide analog, M-PTH(1–11), as well as by the native PTH(1–9) sequence, as tethered to the extracellular end of transmembrane domain (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to within an extracellularly exposed area that is occupied by the N-terminal residues of PTH peptides. Additionally, they suggest that the inhibitory effects of SW106 are limited to the extracellular portions of the TMD region that mediate interactions with agonist ligands but do not extend to receptor-activation determinants situated more deeply in the helical bundle. The study helps to elucidate potential mechanisms of small-molecule binding at the PTHR1.

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