A5091552674- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Insect Resistance and Genetics
- Neuroblastoma Research and Treatments
- Psychoanalysis and Social Critique
- Plant and fungal interactions
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Energy Harvesting in Wireless Networks
- Insect-Plant Interactions and Control
- Molecular Junctions and Nanostructures
- Synthesis and Biological Evaluation
- Blood properties and coagulation
- Inhalation and Respiratory Drug Delivery
- Medical History and Research
- Toxin Mechanisms and Immunotoxins
- Historical Psychiatry and Medical Practices
- Advanced Chemical Sensor Technologies
- Phytoplasmas and Hemiptera pathogens
- Chromium effects and bioremediation
- Plant Surface Properties and Treatments
University of Arizona
2011-2025
Purdue University West Lafayette
2017
Rutgers, The State University of New Jersey
2006
New Mexico State University
1990
Formation of the G-quadruplex in human telomeric sequence can inhibit activity telomerase, thus intramolecular G-quadruplexes have been considered as an attractive anticancer target. Information structures formed under physiological conditions is important for structure-based drug design. Here, we report first structure major a native, non-modified K+ solution. This hybrid-type mixed parallel/antiparallel-G-stranded G-quadruplex, one end which covered by novel T:A:T triple capping structure....
We report the first G-quadruplex structure formed in promoter region of human bcl-2. Bcl-2 is a potent oncoprotein that functions as an inhibitor cell apoptosis and has been found to be aberrantly overexpressed wide range tumors. A highly GC-rich upstream P1 plays important role regulation transcriptional activity bcl-2 oncogene. The purine-rich strand this contains multiple runs guanines can form three distinct intramolecular G-quadruplexes K+-containing solution. Of these, within middle...
Unimolecular parallel-stranded G-quadruplex structures are found to be prevalent in gene promoters. The nuclease hypersensitivity element III(1) (NHE III(1)) of the c-MYC promoter can form transcriptionally active and silenced forms, formation DNA has been shown critical for transcriptional silencing. solution structure a 2:1 quindoline-G-quadruplex complex solved shows unexpected features, including drug-induced reorientation flanking sequences new binding pocket. While both 3' 5' complexes...
Abstract Vascular endothelial growth factor (VEGF) proximal promoter region contains a poly G/C-rich element that is essential for basal and inducible VEGF expression. The guanine-rich strand on this tract has been shown to form the DNA G-quadruplex structure, whose stabilization by small molecules can suppress We report here nuclear magnetic resonance structure of major intramolecular formed in K+ solution using 22mer sequence with G-to-T mutations two loop residues. Our results have...
The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in regulation expression. Inhibition expression can decrease cellular proliferation and enhance efficacy chemotherapy. Here we report major G-quadruplex formed Pu39 G-rich strand this region. 1245G4 quadruplex adopts parallel structure with one 13-nt two 1-nt chain-reversal loops. involves four nonsuccessive G-runs, I, II, IV, V, unlike previously reported bcl2 MidG4...
The abnormal overexpression of the BCL2 gene is associated with many human tumors. We found a new 28-mer G-quadruplex-forming sequence, P1G4, immediately upstream P1 promoter. P1G4 shown to be transcription repressor using promoter-driven luciferase assay; its inhibitory effect can markedly enhanced by G-quadruplex-interactive compound TMPyP4. G-quadruplex readily form in sequence under physiological salt condition as DMS footprinting. and previously identified Pu39 G-quadruplexes appear...
The MYC oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, major MycG4-binding protein, exhibits greater affinity for MycG4 than nucleolin recognition element (NRE) RNA. Nucleolin’s four RNA binding domains (RBDs) are essential high-affinity binding. We present the 2.6-angstrom crystal structure of nucleolin-MycG4 complex, revealing folded parallel three-tetrad with two coordinating potassium ions (K + ), interacting RBD1,...
In our recent published study entitled “Stress granules play a critical role in hexavalent chromium-induced malignancy G3BP1-dependent manner”, we explored how chromium [Cr(VI)] exposure induces stress granule (SG) formation human bronchial epithelial cells and SGs contribute to the malignancy. We found that loss of SG core protein Ras-GAP SH3 domain-binding 1 (G3BP1) reduced malignant properties. The results support mediating Cr(VI)-induced manner, representing novel mechanism potential...
Extracts prepared from floral meristematic tissue of alfalfa (Medicago sativa L.) were investigated for expression the enzyme transglutaminase in order to identify major protein substrate transglutaminase-directed modifications among plant proteins. The large polymorphic subunits ribulose 1,5-bisphosphate carboxylase/oxygenase alfalfa, with molecular weights 52,700 and 57,600, are substrates these extracts. This was established by: (a) covalent conjugation monodansylcadaverine subunit...
RNA interference (RNAi) has potential to become a major tool for integrated management of insect pests agricultural crops based on sequence-specificity and low doses rapidly biodegradable dsRNA. Deploying 'environmental RNAi' control vectors plant pathogens is increasing interest combatting emerging diseases. Hemipteran vectors, including psyllids, are vascular feeders, making their development difficult specifically by targeting with pesticidal chemistries. Psyllids transmit "Candidatus...
Disrupted l-Carnitine (L-Car) homeostasis has been implicated in the development of pulmonary hypertension (PH). L-Car administered orally and intravenously causing systemic side effects. To authors' knowledge, there are no reports using or HCl as an inhaled aerosol through respiratory route a targeted manner either from dry powder inhaler (DPI) liquid delivery system. The purpose comprehensive systematic comparative study between salt was to design develop inhalers (DPIs) each. This...
Double-stranded RNA (dsRNA) biopesticides are of interest for the abatement insect vectors pathogenic bacteria such as 'Candidatus Liberibacter', which infects both its psyllid and plant hosts. Silencing genes essential psyllids, or Liberibacter, is anticipated to lead mortality impeded bacterial multiplication. Foliar delivery preferred biopesticide application; however, cuticle impedes dsRNA penetration into vasculature. Here, conditions were established wounding tomato leaves using...
In probing the mechanism of inhibition hypoxia inducible factor (HIF-1) by campothecins, we investigated ability human topoisomerase I to bind and cleave HIF-1 response element (HRE), which contains known camptothecin-mediated cleavage site 5'-TG. We observed that selection 5'-TG topotecan depends a large extent on specific flanking sequences, presence G at -2 position (where occurs between -1 +1) prevents HRE from being preferred for such cleavage. Furthermore, T/A can induce less TC or TA...
Abstract Abnormal expression of PDGFR-β protein contributes to several malignancies. has become increasingly attractive therapeutic target in the treatments certain cancers. A G-quadruplex-forming nuclease hypersensitive element (NHE) human promoter been found form multiple G-quadruplexes from overlapping sequences. This NHE shown regulate approximately 60% basal activity. Targeting transcriptional control provides an for developing inhibitors signaling pathway, addition molecular targeting...
Abstract Deregulation of bcl-2, an anti-apoptotic protein, is associated with several human diseases such as tumorigenesis, neurodegeneration, and autoimmune deficiencies. DNA G-quadruplex secondary structures that form in the G-rich proximal promoter regions have been found to play important role gene transcriptional regulation. We discovered a novel GC-rich sequence immediate P1 bcl-2 (bcl2P1Pu29), which forms thermodynamically stable, intramolecular (bcl2P1G4) represses transcription....
Abstract The abnormal overexpression of the BCL-2 protein is linked to a large number cancers. Elevated levels are found promote resistance chemotherapy and radiation. Therefore, considered be an attractive target for cancer therapeutics. We have previously identified 39-base-pair GC-rich sequence located in major P1 promoter region human gene, whose G-rich strand (Pu39) can form two interchangeable G-quadruplex (G4) structures, hybrid-type parallel with 13-nt middle loop. However, our...
Abstract ER has emerged as one of the most effective targets for breast cancer therapy since discovery estrogen receptor (ER) modulator action. However, current ER-targeting therapies have a main limitation related to resistance. Our previous studies shown that XR5944, DNA bis-intercalator is capable inhibiting activity by its ability specifically block binding consensus EREs. An intercalator ERE may be useful therapeutic agent can overcome resistance existing endocrine therapies. To...
Abstract Overexpression of the c-Myc oncogene is associated with a broad spectrum human cancers. Targeting transcriptional control represents an attractive means for cancer molecular therapeutics. A highly conserved nuclear hypersensitivity element III1 (NHE III1) promoter controls 80–90% transcription. It can form transcriptionally active and silenced forms, formation DNA G-quadruplex structures has been shown to be critical silencing. Small molecules that stabilize have suppress...
Abstract Since the discovery of estrogen receptor (ER) as modulator action, ER has evolved to be one most effective targets for breast cancer therapy. However, current ER-targeting therapies have a main limitation related resistance. Our previous studies shown that XR5944, DNA bis-intercalator with potent anticancer activity, is capable inhibiting activity by its ability specifically block binding consensus sequence ERE compared other transcription factor-target interactions. This novel...
Abstract Aberrant expression of PDGFR-β promotes multiple hallmarks cancer, and its transcriptional regulation provides an attractive means to inhibit the signaling pathway. The nuclease hypersensitive element (NHE) region human core promoter has been shown be responsible in regulating approximately 60% basal activity. Multiple overlapping G-quadruplexes (G4s) have form this NHE region. We previously determined most stable G4 structure formed 5’-mid Significantly, ellipticine analog,...