A5058636138- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Crystallography and molecular interactions
- Adenosine and Purinergic Signaling
- HIV/AIDS drug development and treatment
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Fluorine in Organic Chemistry
- Synthetic Organic Chemistry Methods
- Mosquito-borne diseases and control
- Cytomegalovirus and herpesvirus research
- Oxidative Organic Chemistry Reactions
- Carbohydrate Chemistry and Synthesis
- Pharmacological Receptor Mechanisms and Effects
- Hepatitis C virus research
- Traditional and Medicinal Uses of Annonaceae
- Pneumocystis jirovecii pneumonia detection and treatment
- Viral Infections and Outbreaks Research
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Cancer-related gene regulation
- HIV/AIDS Research and Interventions
- Biochemical and Molecular Research
- Marine Sponges and Natural Products
- Sulfur-Based Synthesis Techniques
Seoul National University
2017-2025
Seoul Institute
2019
Indian Institute of Technology Bombay
2014-2016
The 6′-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and host cell S-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of RNA. introduction a fluorine 6′-position enhanced inhibition SAH hydrolase activity against viruses. adenosine N6-methyladenosine analogues 2a–e showed potent while only derivatives 2a–c exhibited all tested viruses such Middle East respiratory...
Based on the promising biological activity of 6′-fluorocyclopentenyl-cytosine and -adenine, we report design synthesis 6′-trifluoromethylcyclopentenyl-pyrimidine -purine as potential antiviral agents. The introduction a trifluoromethyl (CF3) group onto sugar scaffold has been achieved using methyl fluorosulfonyldifluoroacetate (Chen's reagent) key step. resulting trifluoromethylated intermediate provides an efficient pathway for synthesizing various nucleoside analogues, facilitating...
Adenosine receptors (ARs) play crucial roles in various physiological processes, making them significant targets for therapeutic intervention. This study focuses on the design, synthesis, and evaluation of N6‐substituted‐C2‐alkynyl‐4′‐thioadenosine truncated 4′‐thioadenosine derivatives as selective ligands human A3 adenosine receptor (hA3 AR). Binding affinity assays demonstrated that modifications at C2‐alkyne N6‐amine positions significantly influenced selectivity potency. Compound 3b...
Modulators of the G protein-coupled A2A adenosine receptor (A2AAR) have been considered promising agents to treat Parkinson's disease, inflammation, cancer, and central nervous system disorders. Herein, we demonstrate that a thiophene modification at C8 position in common adenine scaffold converted an A2AAR agonist into antagonist. We synthesized characterized novel antagonist, 2 (LJ-4517), with Ki = 18.3 nM. X-ray crystallographic structures complex two thermostabilized constructs were...
Alphaviruses are arthropod-borne, positive-stranded RNA viruses capable of causing severe disease with high morbidity. Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness which can progress into chronic arthralgia. The current lack vaccines and specific treatment for CHIKV infection underscores the need to develop new therapeutic interventions. To discover antiviral agents, we performed compound screen in cell culture-based models identified two carbocyclic adenosine...
Based on hA2AAR structures, a hydrophobic C8-heteroaromatic ring in 5′-truncated adenosine analogues occupies the subpocket tightly, converting agonists into antagonists while maintaining affinity toward hA3AR. The final compounds of 2,8-disubstituted-N6-substituted 4′-thionucleosides, or 4′-oxo, were synthesized from d-mannose and d-erythrono-1,4-lactone, respectively, using Pd-catalyst-controlled regioselective cross-coupling reaction. All tested completely antagonized hA2AAR, including 5d...
Triple-negative breast cancer (TNBC) is among the most aggressive and potentially metastatic malignancies. Most affected patients have poor clinical outcomes due to lack of specific molecular targets on tumor cells. The upregulated expression disruptor telomeric silencing 1-like (DOT1L), a histone methyltransferase for H3 lysine 79 residue (H3K79), strongly correlated with TNBC cell aggressiveness. Therefore, DOT1L considered potential target in TNBC. Fluoro-neplanocin A (F-NepA), an...
In search of a new template for anti-hepatitis C virus (HCV) agents, we designed and synthesized the 2′-C-methyl-4′-selenopyrimidine -purine nucleosides their phosphoramidate prodrugs to replace furanose oxygen anti-HCV nucleos(t)ides with selenium atom on basis that is chemical isostere oxygen. These are expected show different physicochemical properties such as better lipophilicity which might enhance penetration across cell membranes conformational constraint induced by bulky in sugar...
Synthesis of a tetracyclic ring system (BCDE) atropurpuran is described. Oxidative dearomatization, cycloaddition spiroepoxycyclohexa-2,4-dienone, radical cyclization, and tandem oxidation–aldol–oxidation are the key features our methodology.
Building on the preceding structural analysis and a structure–activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents eliminated ribose moiety. These modifications aimed to mitigate potential steric interactions between adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending type ribose, whereas removal altered functional efficacy via hA2AAR. Among...
(-)-6'-β-Fluoro-aristeromycin (2), a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, has been synthesized via stereoselective electrophilic fluorination followed by purine base build-up approach. Interestingly, condensation using cyclic sulfate resulted in synthesis (+)-5'-β-fluoro-isoaristeromycin (2a). Computational analysis indicates that the fluorine atom controlled regioselectivity substitution.
We have established a catalyst-dependent regioselective Sonogashira coupling methodology where both regioisomeric products can be obtained independently with remarkably high selectivity.
An alternative and efficient approach to neplanocin A analogs <bold>1b</bold> <bold>1d</bold> has been developed using electrophilic fluorination Pd-catalyzed dehydrosilylation.
The conformation of the central five-membered ring a nucleoside plays an important role in enzyme recognition. Bicyclo[3.1.0]hexane, also known as methanocarba (MC), serves template that can mimic locked forms two distinctive conformations, namely, north and south conformations. While modified nucleosides have been actively investigated, counterpart remains largely unexplored because it is difficult to synthesize. Herein, we report concise synthetic route provide key amino sugar intermediate...
Abstract Intrigued by the biological activity of 2′‐ C ‐methylribofuranosyl nucleosides, and ribavirin/acadesine, based on bioisosteric rationale between oxygen selenium, we herein report a design synthesis ‐methyl‐4′‐seleno‐ribavirin ‐acadesine as potential anti‐HCV agents. The ‐methyl 4′‐selenoribavirin was synthesized in regio‐ stereoselective manner completely characterized through 2D NMR X‐ray crystallography. While 4′‐selenoacadesine has been efficiently utilizing purine‐ring...