The synthesis of the complete family of phosphatidylinositol phosphate analogues (PIPs) from five key core intermediates A-E is described. These core compounds were obtained from myo-inositol orthoformate 1 via regioselective DIBAL-H and trimethylaluminium-mediated cleavages and a resolution-protection process using camphor acetals 10. Coupling of cores A-E with phosphoramidites 34 and 38, derived from the requisite protected lipid side chains, afforded the fully-protected PIPs. Removal of the remaining protecting groups was achieved via hydrogenolysis using palladium black or palladium hydroxide on carbon in the presence of sodium bicarbonate to afford the complete family of dipalmitoyl- and amino-PIP analogues 42, 45, 50, 51, 58, 59, 67, 68, 76, 77, 82, 83, 92, 93, 99 and 100. Investigations using affinity probes incorporating these compounds have identified novel proteins involved in the PI3K intracellular signalling network and have allowed a comprehensive proteomic analysis of phosphoinositide interacting proteins.
Immobilizing chemically synthesized analogues of PI(3,4,5)P3 onto Affi-10 beads and incorporating them into liposomes allowed their use as affinity absorbents in the comprehensive analysis of the phosphoinositide interactome using cytosolic cell extracts of the LIM1215 colon cancer cell line. This led to the identification of 282 proteins that either interact with PI(3,4,5)P3 or are indirectly captured as part of a complex containing a PI(3,4,5)P3 binding partner. Identification of the proteins was achieved using affinity/LC-MS/MS experiments.
Background: Lung cancer (LC) is a complex disease requiring coordination of multiple healthcare professionals. A recently implemented LC Multidisciplinary Clinic (MDC) at Kingston Health Sciences Centre, an academic tertiary care hospital, improved timeliness of oncology assessment and treatment. This study describes patient, caregiver, and physician experiences in the MDC.Methods: We qualitatively studied patient, caregiver, and physician experiences in a traditional siloed care model and in the MDC model. We used purposive sampling to conduct semi-structured interviews with patients and caregivers who received care in either model, and physicians who worked in both models. Thematic design was used to analyze data through open coding in Atlas-ti.Results: Six of the 72 identified patients from the traditional model, and 6 of the 40 identified patients from the MDC model, participated. Caregivers were encouraged to join patient interviews. Eight of nine physicians who provided care in both models were interviewed (2 respirologists, 2 medical oncologists, 4 radiation oncologists). Four themes emerged: communication and collaboration, efficiency, quality of care, and impact on patient outcomes. Patients in both models had positive impressions of their care. MDC patients frequently reported convenience and a positive impact of family presence at appointments. Physicians reported that the MDC improved communication and collegiality, clinic efficiency, patient outcomes and satisfaction, and consistency of information provided to patients. Physicians identified lack of clinic space as an area for improvement in the MDC. Conclusions: This exploratory study informs our understanding of the effects of change in a multidisciplinary healthcare delivery model by directly studying those involved.
Cardiolipin (1) is a dimeric phospholipid found in the mitochondrial membranes of both plants and animals. In order to understand better its role, we report the preparation of an immobilised analogue (2) using phosphoramidite chemistry; the probe has been used successfully to bind a recombinant protein containing a cardiolipin-binding domain.
An enantiopure amine tris(phenolate) ligand containing a single stereogenic center has been used to control the propeller-like chirality of a derived pseudo-C3-symmetric titanium isopropoxide complex with excellent levels of diastereocontrol. [structure: see text].
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