Synthesis of Chiral (α,α-Difluoroalkyl)phosphonate Analogues of (Lyso)phosphatidic Acid via Hydrolytic Kinetic Resolution

Xu, Yu; Prestwich, Glenn D.

doi:10.1021/ol026684s

Cited by 47 publications

(49 citation statements)

References 53 publications

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“…Steady-state PLASMA LPA levels are normally low (less than 100 nM) 86,87,94,95 , representing the equilibrium between production, degradation and clearance. Unidentified factors in plasma and seminal fluid seem to inhibit LPA activity 87,96 .…”

Section: Extracellular Metabolism Of Lpamentioning

confidence: 99%

“…A similar approach showed aberrations in particular LPC isoforms in plasma from ovarian cancer patients 122 . More recent studies using a massspectrometry approach failed to detect increased levels of LPA in plasma from ovarian cancer patients or alterations in levels of particular isoforms 95 , although even this finding is controversial 12,124 . An analysis of ATX/lysoPLD activity failed to detect aberrant activity in blood samples from ovarian cancer patients 125 .…”

Section: Lysophospholipids As Tumour Markersmentioning

confidence: 99%

“…Ascites fluid is a potent mitogen for ovarian cancer cells in vitro and in vivo [113][114] . A significant portion of this activity is mediated by LPA, which is present in ascites fluid at between 1 and 80 µM, exceeding levels required to optimally activate LPA receptors 70,95,[115][116][117] . LPA is not produced at significant levels by normal ovarian epithelial cells, whereas ovarian cancer cells produce increased levels of LPA 69,118 .…”

Section: Lpa In the Pathophysiology Of Cancermentioning

confidence: 99%

“…Indeed, a series of secreted and transmembrane ecto-enzymes are crucial for the production and metabolism of extracellular LPA [86][87][88][89][90][91][92][93] (FIGS 1,3). Steady-state PLASMA LPA levels are normally low (less than 100 nM) 86,87,94,95 , representing the equilibrium between production, degradation and clearance. Unidentified factors in plasma and seminal fluid seem to inhibit LPA activity 87,96 .…”

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confidence: 99%

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Detection of Serum Lysophosphatidic Acids Using Affinity Binding and Surface Enhanced Laser Deorption/Ionization (SELDI) Time of Flight Mass Spectrometry

Mills¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) 01-04-2006 REPORT TYPE SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains color plates: All DTIC reproductions will be in black and white. ABSTRACTWe proposed to apply novel technologies to the development of an approach suitable to detect plasma and serum lipid levels for screening for ovarian cancer in high and low risk women. The first of these is a novel approach to the development of antibodies, which will recognize specific phospholipids and lysophospholipids present in ovarian cancer patients and the second of these is SELDI tof mass spectroscopy. These two technologies will be merged with powerful computing tools to develop approaches capable of detecting ovarian cancer at an early, curable stage. This approach will further benefit from the expertise of the Mills laboratory (LPA screening, SELDI tof) with that of the Prestwich laboratory (lipid synthesis and antibody development). Results We have completed the studies proposed in the application. We have demonstrated that SELDI mass spectroscopy using nonspecific and affinity matrices has the ability to detect and characterize model lysopholipids including LPC, LPA, S1P and LPS present in plasma and serum. This assay is applicable to relatively large volumes of plasma and serum >2ml. We have also demonstrated that additional mass spectroscopy approaches have a greater degree of sensitivity and specificity when compared to SELDI mass spectroscopy. We proposed to develop and analyze lipid specific antibodies. We have analyzed anti-S1P antibodies as both a theragnostic and a diagnostic using a sensitive ELISA approach. LPA antibodies appear to block the growth of hybridomas due to blocking LPAmediated survival. We thus took an interim step of identifying novel LPA binding proteins as alternative affinity reagents. We also developed novel LPA receptor selective ...

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Section: Extracellular Metabolism Of Lpamentioning

confidence: 99%

Section: Lysophospholipids As Tumour Markersmentioning

confidence: 99%

Section: Lpa In the Pathophysiology Of Cancermentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of Serum Lysophosphatidic Acids Using Affinity Binding and Surface Enhanced Laser Deorption/Ionization (SELDI) Time of Flight Mass Spectrometry

Mills¹

2006

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“…The mechanism of the reaction has proven to involve cooperative bimetallic catalysis. [3][4][5][6][7][8][9] Many groups have devoted their efforts to developing heterogeneous analogs of the typical salen-Co(III) catalyst including organic or inorganic supported catalysts, 10-12 dimeric catalysts, 13 dendrimeric catalysts, 14 oligomeric catalysts, 15,16 FBS (Fluorous Biphase Systems) 17 and ionic liquid 18 for both academic and practical reasons. Among those reports mentioned above, Jacobsen's oligomeric catalysts (Fig.…”

mentioning

confidence: 99%

Highly enantioselective resolution of terminal epoxides with cross-linked polymeric salen–Co(III) complexes

Song

Chen

et al. 2003

Tetrahedron Letters

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Synthesis of γ‐Hydroxy‐α,α‐difluoromethylenephosphonates

Kazakova

Röschenthaler

2012

Efficient Preparations of Fluorine Compounds

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Synthesis of Chiral (α,α-Difluoroalkyl)phosphonate Analogues of (Lyso)phosphatidic Acid via Hydrolytic Kinetic Resolution

Cited by 47 publications

References 53 publications

Detection of Serum Lysophosphatidic Acids Using Affinity Binding and Surface Enhanced Laser Deorption/Ionization (SELDI) Time of Flight Mass Spectrometry

Detection of Serum Lysophosphatidic Acids Using Affinity Binding and Surface Enhanced Laser Deorption/Ionization (SELDI) Time of Flight Mass Spectrometry

Highly enantioselective resolution of terminal epoxides with cross-linked polymeric salen–Co(III) complexes

Synthesis of γ‐Hydroxy‐α,α‐difluoromethylenephosphonates

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