A5101472065- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Cardiac Fibrosis and Remodeling
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Crystallography and molecular interactions
- Peptidase Inhibition and Analysis
- NF-κB Signaling Pathways
- Signaling Pathways in Disease
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Molecular Sensors and Ion Detection
- RNA modifications and cancer
- Supramolecular Chemistry and Complexes
- RNA regulation and disease
- interferon and immune responses
- Cardiac Ischemia and Reperfusion
- Phytoestrogen effects and research
- Metal-Organic Frameworks: Synthesis and Applications
- Supramolecular Self-Assembly in Materials
- Covalent Organic Framework Applications
- Mitochondrial Function and Pathology
- Digestive system and related health
University of Notre Dame
2024-2025
Nanyang Technological University
2018-2024
GITAM University
2022
Sree Chitra Thirunal Institute for Medical Sciences and Technology
2007-2016
Indian Institute of Technology Kanpur
2014-2015
University of Hyderabad
2011
Institute of Life Sciences
2011
Universiti Sains Malaysia
1999
Concurrent construction of five and six membered fused N-heretocyclic ring was achieved via a conceptually new three-component reaction affording 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-diones as novel inhibitors TNF-αin vitro. This represents one the few examples direct TNF-α inhibition by small molecules.
RNAs play critical roles in diverse catalytic and regulatory biological processes are emerging as important disease biomarkers therapeutic targets. Thus, developing chemical compounds for targeting any desired RNA structures has great potential biomedical applications. The viral cellular sequence structure databases lay the groundwork RNA-binding ligands through recognition of both structure. Influenza A virion consists eight segments negative-strand (vRNA), all which contain a highly...
An Mn metal-organic framework (Mn-MOF), Mn-L, based on a pyrene-tetraacid linker (H4 L), displays respectable fluorescence quantum yield of 8.3% in spite the presence paramagnetic metal ions, due presumably to fixation ions geometries that do not allow complete energy/charge-transfer quenching. Remarkably, porous Mn-L MOF with ∼25% solvent-accessible volume exhibits heretofore unprecedented solvent-dependent emission maximum, permitting its use as probe solvent polarity; maxima different...
Cardiac fibroblast hyperplasia associated with enhanced matrix deposition is a major determinant of tissue remodeling in several disease states the heart. However, mechanisms controlling cell cycle progression cardiac fibroblasts remain unexplored. Identification regulatory elements these cells important to develop strategies check adverse under pathological conditions. This study sought probe underlying ERK1/2-mediated p27 Kip1 regulation mitogenically stimulated fibroblasts. Addition 10%...
Double-stranded RNA (dsRNA) structures form triplexes and RNA-protein complexes through binding to single-stranded (ssRNA) regions proteins, respectively, for diverse biological functions. Hence, targeting dsRNAs major-groove triplex formation is a promising strategy the development of chemical probes potential therapeutics. Short (e.g., 6-10 mer) chemically-modified Peptide Nucleic Acids (PNAs) have been developed that bind sequence specifically at physiological conditions. For example, PNA...
Dysregulated adenosine-to-inosine (A-to-I) RNA editing is implicated in various cancers. However, no available inhibitors have so far been developed to inhibit cancer-associated events. Here, we decipher the secondary structure of antizyme inhibitor 1 (AZIN1), one best-studied A-to-I targets cancer, by locating its site complementary sequence (ECS) at 3′ end exon 12. Chemically modified antisense oligonucleotides (ASOs) that target region AZIN1 caused a substantial 11 skipping, whereas...
Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA with 3ʹ-terminal triple helix, which stabilizes and protects the from degradation. This stabilization contributes to MALAT1 overaccumulation, promoting cancer disease. The unique structure function of helix makes it an ideal target for small-molecule intervention. Yet, structural details regarding interactions between small molecule drug remain unclear. Herein, I aim solve 3D in complex diminazene...
Minus-one programmed ribosomal frameshifting (−1 PRF) allows the precise maintenance of ratio between viral proteins and is involved in regulation half-lives cellular mRNAs. activated by several stimulatory elements such as a heptameric slippery sequence (X XXY YYZ) an mRNA secondary structure (hairpin or pseudoknot) that positioned 2–8 nucleotides downstream from site. Upon −1 RF, reading frame shifted normal zero to with decoded XXX YYY Z instead X YYZ. Our research group has developed...
Chemically modified peptide nucleic acids (PNAs) show great promise in the recognition of RNA duplexes by major-groove PNA·RNA–RNA triplex formation. Triplex formation is favored for with a purine tract within one duplex strands, and severely destabilized if interrupted pyrimidine residues. Here, we report synthesis PNA monomer incorporated an artificial nucleobase S, followed binding studies series S-modified PNAs. Our data suggest that S residue into short 8-mer dsRNA-binding PNAs (dbPNAs)...
RNAs are emerging as important biomarkers and therapeutic targets. The strategy of directly targeting double-stranded RNA (dsRNA) by triplex-formation is relatively underexplored mainly due to the weak binding at physiological conditions for traditional triplex-forming oligonucleotides (TFOs). Compared DNA RNA, peptide nucleic acids (PNAs) chemically stable have a neutral peptide-like backbone, thus, they show significantly enhanced natural acids. We successfully developed...
Chemically modified short peptide nucleic acids (PNAs) recognize RNA duplexes under near physiological conditions by major-groove PNA·RNA–RNA triplex formation and show great promise for the development of RNA-targeting probes therapeutics. Thymine (T) uracil (U) are often incorporated into PNAs to A-U pairs through T·A-U U·A-U base triple formation. Incorporation a nucleobase, 2-thiouracil (s2U), triplex-forming oligonucleotides stabilizes both DNA triplexes. Thiolation causes decrease in...
Cardiac fibroblasts contribute to multiple aspects of myocardial function and pathophysiology. The pathogenetic relevance cytokine production by these cells under hypoxia, however, remains unexplored. With the use an in vitro cell culture model, this study evaluated hypoxic cardiac examined two distinct effects fibroblast-conditioned medium (HFCM) on myocytes fibroblasts. Hypoxia caused a marked increase tumor necrosis factor (TNF)-α HFCM significantly enhanced susceptibility reactive oxygen...
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine neoplasia-β (MENβ) are two long noncoding RNAs upregulated in cancers, marking these as therapeutic targets. While traditional small-molecule antisense-based approaches effective, we report a locked nucleic acid (LNA)-based approach that targets the MALAT1 MENβ triple helices, structures comprised of U-rich internal stem-loop an A-rich tract. Two LNA oligonucleotides resembling tract (i.e., A9GCA4) were...
Recognition of RNAs under physiological conditions is important for the development chemical probes and therapeutic ligands. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) are promising recognition dsRNAs in a sequence structure specific manner near-physiological conditions. Guanidinium often present proteins small molecules G bases nucleic acids, cell-penetrating carriers, bioactive drug molecules, which might be due to fact that guanidinium amphiphilic has unique hydrogen bonding stacking...
The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of unique binding pocket at 5′ side human telomeric G-quadruplex (HTG) sequence four repeats (Q4), resulting in nanomolar affinity (KD approximately 26 nM) significant fluorescence enhancement upon binding. It important to understand (1) how affects HTG structural stability (2) enhanced may be achieved through...
RNA secondary structures comprise double-stranded (ds) and single-stranded (ss) regions. Antisense peptide nucleic acids (asPNAs) enable the targeting of ssRNAs weakly formed dsRNAs. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) allow for dsRNA targeting. A programmable RNA-structure-specific strategy is needed simultaneous recognition dsRNAs ssRNAs. Here, we report on combining dbPNAs asPNAs (designated as daPNAs) dsRNA-ssRNA junctions. Our data suggest that traditional asPNA (with a...
Minor-groove base triples formed between stem 1 and loop 2 of the simian retrovirus type (SRV-1) mRNA frameshifting pseudoknot are essential in stimulating −1 ribosomal frameshifting. How tertiary triple formation affects local stabilities secondary structures (stem 2) thus efficiency is not well understood. We made a short peptide nucleic acid (PNA) that expected to invade SRV-1 by PNA–RNA duplex mimic unwinding process translating ribosome. In addition, we used PNA for invading pseudoknot....
Abstract An efficient and simple synthesis of various 3-(trifluoromethyl)chromones from enamino ketones is described. The key step in the involves introduction a trifluoromethyl (CF3) moiety onto chromone structure. significant features this method include operational procedures, high purity yield product, excellent regioselectivity.