16 research outputs found
ChemInform Abstract: Functionalization of Non‐Activated C—H Bonds in the Synthesis of Vitamin D Metabolites and Analogues
No full textSynthesis, structure, and biological activity of des-side Chain analogues of 1α,25-Dihydroxyvitamin D3 with substituents at C18
No full textAn improved synthetic route to 1α,25-dihydroxyvitamin D3 des-side chain analogues 2a and 2b with substituents at C18 is reported, along with their biological activity. These analogues display significant antiproliferative effects toward MCF-7 breast cancer cells and prodifferentiation activity toward SW480-ADH colon cancer cells; they are also characterized by a greatly decreased calcemic profile. The crystal structure of the human vitaminD receptor (hVDR) complexed to one of these analogues, 20(17→18)-abeo-1α,25-dihydroxy-22-homo-21-norvitamin D3 (2a) reveals that the side chain introduced at position C18 adopts the same orientation in the ligand binding pocket as the side chain of 1α,25-dihydroxyvitamin D3. Vitamin D3 supplements: The synthesis and biological activity of des-side chain analogues of 1α,25-dihydroxyvitamin D3 with substituents at C18 are described. Crystallographic analysis revealed that the new side chain introduced at C18 adopts the same orientation as the natural side chain at C17 in the parent molecule 1α,25-dihydroxyvitamin D3. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Fil: Verlinden, Lieve. Katholikie Universiteit Leuven; BélgicaFil: Verstuyf, Annemieke. Katholikie Universiteit Leuven; BélgicaFil: Eelen, Guy. Katholikie Universiteit Leuven; BélgicaFil: Bouillon, Roger. Katholikie Universiteit Leuven; BélgicaFil: Ordóñez-Morán, Paloma. Universidad Autónoma de Madrid; EspañaFil: Larriba, María Jesús. Universidad Autónoma de Madrid; EspañaFil: Muñoz, Alberto. Universidad Autónoma de Madrid; EspañaFil: Rochel, Natacha. Université de Strasbourg; FranciaFil: Sato, Yoshiteru. Université de Strasbourg; FranciaFil: Moras, Dino. Université de Strasbourg; FranciaFil: Maestro, Miguel. Universidad da Coruña; EspañaFil: Seoane, Samuel. Universidad de Santiago de Compostela, Facultad de Medicina;Fil: Dominguez, Fernando. Universidad de Santiago de Compostela, Facultad de Medicina;Fil: Eduardo, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Santiago de Compostela; EspañaFil: Nicoletti, Daniel. Universidad de Santiago de Compostela; EspañaFil: Moman, Edelmiro. Universidad de Santiago de Compostela; EspañaFil: Mouriño, Antonio. Universidad de Santiago de Compostela; Españ
Strained Polycycles by H<sup>5</sup>C<sup>5x</sup> Free-Radical Cascades<sup>†</sup>
No full textAn H5C5x-type free-radical chain reaction selectively generates up to three new bonds and three new stereocenters in one pot. This previously
unexploited strategy provides a straightforward route to the tricyclic cyclopenta[c]indene skeleton, present in a wide range of pharmacologically
active natural products, and can significantly simplify the synthesis of other strained polycyclic structures by sidestepping protection,
deprotection, and functional group interconversion steps
Strained Polycycles by H<sup>5</sup>C<sup>5x</sup> Free-Radical Cascades<sup>†</sup>
No full textAn H5C5x-type free-radical chain reaction selectively generates up to three new bonds and three new stereocenters in one pot. This previously
unexploited strategy provides a straightforward route to the tricyclic cyclopenta[c]indene skeleton, present in a wide range of pharmacologically
active natural products, and can significantly simplify the synthesis of other strained polycyclic structures by sidestepping protection,
deprotection, and functional group interconversion steps
Evaluation of fecal and serum ASCA as predictors of relapse in patients suspected of having inflammatory bowel disease
No full textThesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.Background: Patients with Crohn disease (CD) or ulcerative colitis (UC) present with chronic inflammation and have a variety of complaints that can overlap with non-inflammatory gastrointestinal disorders. Non-invasive and inexpensive biomarkers can help elucidate the cause of a patient's symptoms. In addition, some biomarkers are thought to provide predictive value of disease activity. Data indicate that the non-specific biomarker, fecal lactoferrin (FLA), is helpful in diagnosis of gastrointestinal inflammation and is thought to have utility as a predictor of flare in patients with CD or UC. Data from other studies indicate that serum anti-Saccharomyces cerevisiae antibodies (ASCA) levels, while elevated in patients with CD, remains stable over time and are less useful for interval disease assessment. Data from an unpublished pilot study conducted at the Center for Inflammatory Bowel Diseases at Children's Hospital Boston suggests that fecal ASCA is elevated in patients with CD and may change over time. We now hypothesize that fecal ASCA may be a predictor of disease activity in patients with Inflammatory Bowel Disease (IBD).
Methods: Stool samples were collected from 43 patients diagnosed with IBD, 27 diagnosed with CD, and 16 diagnosed with UC. Serum samples were collected from 39 patients diagnosed with IBD, 25 with CD, and 14 with UC. Only patients that were inactive for the previous three months before giving their sample were included. Data collected from patients that experienced a relapse of their disease within 12 months of giving their sample were compared to the group of patients that remained in remission. Each sample was tested for the level of FLA, as well as serum and fecal ASCA.
Results: Seven of the 27 patients diagnosed with CD and six of the 16 patients diagnosed with UC experienced a flare within 12 months of providing their serum and stool samples. Patients with IBD that maintained remission had a median FLA level that was less than that observed in patients that went on to experience a clinical relapse, but this difference displayed borderline statistical significance (P-value of Wilcoxon test =0.06). The AUC-ROC for FLA was 0.67 and it had a sensitivity of 69% and specificity of 59%.
The median fecal ASCA level observed in the group of patients that remained in clinical remission was less than that observed in the group of patients that went on to experience a clinical flare. The difference between the two groups was statistically significant (P-values of Wilcoxon test = 0.0016). The AUC-ROC for fecal ASCA was only 0.58 due to overlap between the two groups.
The group of patients that remained in clinical remission had a median serum ASCA reading that was less than the group of patients that became active. The difference in serum ASCA readings between the two groups was statistically significant (P-values of Wilcoxon test = 0.0044); the AUC-ROC was 0.57.
Conclusions: This study indicates that fecal ASCA may have utility as a predictive biomarker of disease activity in IBD. A future study will investigate fecal ASCA as a predictor of activity for patients specifically with Crohn disease
ChemInform Abstract: Design, Synthesis and Evaluation of Aspirin Analouges Having an Additional Carboxylate Substituent for Antithrombotic Activity.
No full textThe Productive Conformation of Prostaglandin G<sub>2</sub> at the Peroxidase Site of Prostaglandin Endoperoxide H Synthase: Docking, Molecular Dynamics, and Site-Directed Mutagenesis Studies<sup>†</sup>
No full textWe present a plausible productive conformation obtained by docking calculations for the binding
of prostaglandin G2 (PGG2) to the peroxidase site of prostaglandin endoperoxide H synthase-1 (PGHS-1,
COX-1). The enzyme−substrate complex stability was verified by molecular dynamics. Structural analysis
reveals the requirements for enzyme−substrate recognition and binding: the PGG2 15-hydroperoxide
group is in the proximity of the heme iron and participates in a hydrogen bond network with the conserved
His207 and Gln203 and a water molecule, whereas the carboxylate group forms salt bridges with the
remote Lys215 and Lys222. Site-directed mutagenesis showed that a single mutation of Lys215 or Lys222
does not affect enzyme activity, whereas dual mutation of these residues, to either alanine or glutamate,
significantly decreases turnover. This indicates that the conserved cationic pocket is involved in enzyme−substrate binding
Observation of an unusual electronically distorted semiquinone radical of PCB metabolites in the active site of prostaglandin H synthase-2
No full text
