A5062866344- 14-3-3 protein interactions
- Microbial Natural Products and Biosynthesis
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Redox biology and oxidative stress
- Steroid Chemistry and Biochemistry
- Enzyme Structure and Function
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Cancer, Hypoxia, and Metabolism
- Polyomavirus and related diseases
- thermodynamics and calorimetric analyses
- Neuropeptides and Animal Physiology
- Synthesis of Organic Compounds
- Viral-associated cancers and disorders
- Folate and B Vitamins Research
- Pharmacy and Medical Practices
- Educational Leadership and Innovation
- Protein Tyrosine Phosphatases
- Cytokine Signaling Pathways and Interactions
- Innovative Teaching Methods
- ATP Synthase and ATPases Research
- Traditional and Medicinal Uses of Annonaceae
Universiti Sains Malaysia
2012-2025
Monash University
2014-2019
University of Malaya
2012
Hospital Universiti Sains Malaysia
2012
The protein SPSB2 mediates proteosomal degradation of inducible nitric oxide synthase (iNOS). Inhibitors SPSB2-iNOS interaction may prolong the lifetime iNOS and thereby enhance killing persistent pathogens. We have designed a cyclic peptide, Ac-c[CVDINNNC]-NH2, containing key sequence motif mediating interaction, which binds to binding site on with Kd 4.4 nM, as shown by SPR, [(1)H,(15)N]-HSQC, (19)F NMR. An in vitro assay macrophage cell lysates showed complete inhibition interactions...
Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity the FRα active site provides basis designing more specific targets FRα. Heterocyclic rings have been shown interact with receptors and are important metabolism processes within body. Nineteen FA analogs substitution various heterocyclic were designed higher toward Molecular docking was used study of compared FA,...
Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as biological marker in cancer drug delivery. The binding affinity folic acid (FA) to the FRα active site provides basis for recognition FRα. In this study, FA was conjugated beta-cyclodextrin (βCD) and subjected silico analysis (molecular docking molecular dynamics (MD) simulation (100 ns)) investigate stability system compared unconjugated apo systems (ligand free). Docking...
Selective blockade of the serotonin 5‐HT 2A receptor is a useful therapeutic approach for number disorders, including schizophrenia, insomnia and ischaemic heart disease. A series aporphines were docked into homology model rat using AutoDock. Selected compounds with high in silico binding affinities screened vitro radioligand‐binding assays against (5‐HT 1A ) dopamine (D1 D2) receptors. ( R )‐Roemerine (±)‐nuciferine found to have affinity K i = 62 139 n m , respectively), )‐roemerine...
SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression inducible nitric oxide synthase (iNOS) and enhanced killing persistent pathogens, suggesting that inhibitors the SPSB2-iNOS interaction potential as novel anti-infectives. In this study, we describe design, synthesis, characterization cyclic peptidomimetic constrained by organic linkers improve stability druggability. SPR, ITC, (19)F NMR analyses...
SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors SPSB2-iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing persistent pathogens. Here, we describe synthesis characterization two redox-stable cyclized peptides containing DINNN motif required for binding. Both analogues bind with low nanomolar affinity binding site on SPSB, as determined by SPR (19)F NMR, efficiently displace full-length from in macrophage cell lysates. These provide a foundation...
SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated targeted for degradation. Inhibition of this interaction increases levels, consequently cellular (NO) concentrations, has been proposed as a potential strategy killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 CP2) potent inhibitors murine SPSB–iNOS interaction. In study, we report...
Cell-penetrating peptides are used in the delivery of and biologics, with some cell-penetrating found to be more efficient than others. The exact mechanism how they interact cell membrane penetrate it, however, remains unclear. This study attempts investigate difference free energy profiles three (TAT, CPP1 CPP9) a model lipid bilayer (DOPC) using molecular dynamics pulling simulations umbrella sampling. Potential mean force (PMF) barrier between DOPC determined WHAM analysis MM-PBSA...
SPRY domain-containing SOCS box proteins SPSB1, 2, and 4 mediate the proteasomal degradation of inducible nitric oxide synthase (iNOS) thereby modulate amount NO available for combating infectious organisms. A highly conserved Asp-Ile-Asn-Asn-Asn (DINNN) motif found at N-terminus iNOS binds to SPSB2 with nanomolar affinity. The design specific potent inhibitors iNOS–SPSB interactions will be aided by a better understanding this DINNN sequence SPSB2. Although crystal structures SPSB complexes...
Introduction: In the context of pharmacy education worldwide and in Malaysia, use digital technologies to promote higher level thinking discussions is seen as preparing millennials pharmacists 21st century. Together with leveraging on millennials' penchant for mobile technology, gamified online quizzes an assessment tool that help active collaborative learning a Medicinal Chemistry course have been used. Objectives: This study investigates students’ perception impact their course. Method:...
14-3-3σ protein is one of the seven isoforms from highly conserved eukaryotic 14-3-3 family. Downregulation expression has been observed in various tumors. TRIM25 responsible for proteolytic degradation 14-3-3σ, which abrogation suppressed tumor growth through upregulation. However, to date, exact interacting residues have yet be resolved. Thus, this study attempts identify peptide binding sequence on via both bioinformatics and biophysical techniques. Multiple alignment CC domain revealed...
14-3-3 sigma is a vital negative cell cycle regulator. Its expression consistently downregulated in many types of cancer through gene promoter hypermethylation or proteasomal degradation. needs to form homodimer be functional, while dimers are less prone degradation than monomers. This suggests that stabilizer may increase the tumor suppressive activities sigma. However, no known has been reported date. Therefore, this study attempts test potential capability GCP-Lys-OMe (previously bind at...
14-3-3σ plays an important role in controlling tumor metabolic reprogramming and cancer cell growth. However, its function is often compromised many cancers due to downregulation. Previous studies found that homodimerization of critical for activity. date, it not known if stabilization homodimers can improve activity or prevent degradation. In our previous work, we have showed GCP-Lys-OMe a potential homodimer stabilizer. stabilizing effect was experimentally validated. Therefore, this...
An aurone bearing two amine functionalities 12a is a micromolar SHIP2 inhibitor with glucose uptake-enhancing property in rat myotubes. showed good permeability across the Caco-2 cell monolayer indicating its potential as an oral insulin sensitizer.