3 research outputs found
Highly sensitive and selective determination of Hg<sup>2+</sup> by using 3-((2-(1H-benzo[<i>d</i>]imidazol-2-yl)phenylimino)methyl)benzene-1,2-diol as fluorescent chemosensor and its application in real water sample
<div><p>A new receptor 3-((2-(1H-benzo[<i>d</i>]imidazol-2-yl)phenylimino)methyl)benzene-1,2-diol (<b>1</b>) was synthesised and developed as a highly selective fluorescent chemosensor for the detection of Hg<sup>2+</sup> in semi-aqueous media. The fluorescence of receptor <b>1</b> was dramatically and selectively quenched on complexation with Hg<sup>2+</sup> ion with the detection limit down to 0.20 μM. The developed sensor was successfully applied for the determination of Hg<sup>2+</sup> content in water samples. Density Functional Theory (DFT) calculations were performed to study the mechanistic behaviour behind the binding of Hg<sup>2+</sup> with receptor <b>1</b>.</p></div
DataSheet_1_Immunogenicity of two COVID-19 vaccines used in India: An observational cohort study in health care workers from a tertiary care hospital.docx
COVID-19 pandemic witnessed rapid development and use of several vaccines. In India, a country-wide immunization was initiated in January 2021. COVISHIELD, the chimpanzee adenoviral-vectored vaccine with full-length SARS-COV-2 spike insert and COVAXIN, the whole virus-inactivated vaccines were used. To assess and compare immune response of health-care-workers to COVISHIELD (n=187) and COVAXIN (n=21), blood samples were collected pre-vaccination, 1month post-1/post-2 doses and 6months post-dose-2 and tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab,PRNT50) antibodies. Spike-protein-specific T cells were quantitated by IFN-γ-ELISPOT. In pre-vaccination-antibody-negative COVISHIELD recipients (pre-negatives, n=120), %Nab seroconversion (median, IQR Nab titers) increased from 55.1% (16, 2.5-36.3) post-dose-1 to 95.6% (64.5, 4.5-154.2, p<0.001) post-dose-2 that were independent of age/gender/BMI. Nab response was higher among pre-positives with hybrid immunity at all-time points (p<0.01-0.0001) and independent of age/gender/BMI/Comorbidities. Post-dose-2-seroconversion (50%, p<0.001) and Nab titers (6.75, 2.5-24.8, p<0.001) in COVAXIN-recipients were lower than COVISHIELD. COVAXIN elicited a superior IFN-γ-T cell response as measured by ELISPOT (100%; 1226, 811-1532 spot forming units, SFU/million PBMCs v/s 57.8%; 21.7,1.6-169.2; p<0.001). At 6months, 28.3% (15/53) COVISHIELD and 3/3COVAXIN recipients were Nab-negative. T cell response remained unchanged. During immunization, COVID-19 cases were detected among COVISHIELD (n=4) and COVAXIN (n=2) recipients. At 6months, 9cases were recorded in COVISHIELD-recipients. This first-time, systematic, real-world assessment and long-term follow up revealed generation of higher neutralizing antibody titers by COVISHIELD and stronger T-cell response by COVAXIN. Diminished Nab titers at 6months emphasize early booster. Immunogenicity/efficacy of vaccines will change with the progression of the pandemic needing careful evaluations in the field-settings.</p
Characterization of Two Distinct Modes of Drug Binding to Human Intestinal Fatty Acid Binding Protein
The aqueous cytoplasm of cells poses
a potentially significant
barrier for many lipophilic drugs to reach their sites of action.
Fatty acid binding proteins (FABPs) bind to poorly water-soluble fatty
acids (FAs) and lipophilic compounds and facilitate their intracellular
transport. Several structures of FA in complex with FABPs have been
described, but data describing the binding sites of other lipophilic
ligands including drugs are limited. Here the environmentally sensitive
fluorophores, 1-anilinonapthalene 8-sulfonic acid (ANS), and 11-dansylamino
undecanoic acid (DAUDA) were used to investigate drug binding to human
intestinal FABP (hIFABP). Most drugs that bound hIFABP were able to
displace both ANS and DAUDA. A notable exception was ketorolac, a
non-steroidal anti-inflammatory drug that bound to hIFABP and displaced
DAUDA but failed to displace ANS. Isothermal titration calorimetry
revealed that for the majority of ligands including FA, ANS, and DAUDA,
binding to hIFABP was exothermic. In contrast, ketorolac binding to
hIFABP was endothermic and entropy-driven. The X-ray crystal structure
of DAUDA–hIFABP revealed a FA-like binding mode where the carboxylate
of DAUDA formed a network of hydrogen bonds with residues at the bottom
of the binding cavity and the dansyl group interacted with residues
in the portal region. In contrast, NMR chemical shift perturbation
(CSP) data suggested that ANS bound only toward the bottom of the
hIFABP cavity, whereas ketorolac occupied only the portal region.
The CSP data further suggested that ANS and ketorolac were able to
bind simultaneously to hIFABP, consistent with the lack of displacement
of ANS observed by fluorescence and supported by a model of the ternary
complex. The NMR solution structure of the ketorolac–hIFABP
complex therefore describes a newly characterized, hydrophobic ligand
binding site in the portal region of hIFABP