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Title: The synthetic preparation and physical behaviour of phosphatidylinositol-4-phosphates
Author: Furse, Samuel
ISNI:       0000 0004 2700 1337
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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The current set of three studies comprises preparative synthetic organic chemistry, membrane biophysics, and enzymology. Specifically, racemic and chiral synthetic organic preparations of distearoylphosphatidylinositol-4-phosphate (DSPIP) are described, along with tangential studies that inform use of protecting group strategies and the limits and behaviour of key myo-inositol-based intermediates. The biophysical behaviour of this lipid as a function of temperature, pressure, and concentration in dioleoyl phosphatidylcholine and hydration has been examined. Unsaturated analogues of DSPIP, comprising oleoyl (SOPIP) and γ-linolenoyl (SGPIP) have also been prepared, both racemically and chirally. The Enzymology study comprised kinetic assays of the three enantio-pure lipids DSPIP, SOPIP and SGPIP prepared in the organic study with Salmonella (bacterial) phosphatase SopB and has established that increasing numbers of unsaturated bonds in the glyceride residue of the inositide has a decreasing effect on activity of the enzyme and are in agreement with previous preliminary results for this enzyme. This body of work provides further evidence that the sensitivity of biological systems to fatty acids is primarily physical.
Supervisor: Templer, Richard ; Ces, Oscar ; Woscholski, Rudiger Sponsor: Engineering and Physical Sciences Research Council ; Membrane Biophysics Platform Grant
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral