Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes.
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-protect...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2010
|
| _version_ | 1826265976036917248 |
|---|---|
| author | Conway, S Gardiner, J Grove, S Johns, M Lim, Z Painter, G Robinson, D Schieber, C Thuring, J Wong, L Yin, M Burgess, A Catimel, B Hawkins, P Ktistakis, N Stephens, L Holmes, AB |
| author_facet | Conway, S Gardiner, J Grove, S Johns, M Lim, Z Painter, G Robinson, D Schieber, C Thuring, J Wong, L Yin, M Burgess, A Catimel, B Hawkins, P Ktistakis, N Stephens, L Holmes, AB |
| author_sort | Conway, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:31:58Z |
| format | Journal article |
| id | oxford-uuid:3159ee85-d309-4d5a-8b16-b4112dd35dac |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:31:58Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:3159ee85-d309-4d5a-8b16-b4112dd35dac2022-03-26T13:07:26ZSynthesis and biological evaluation of phosphatidylinositol phosphate affinity probes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3159ee85-d309-4d5a-8b16-b4112dd35dacEnglishSymplectic Elements at Oxford2010Conway, SGardiner, JGrove, SJohns, MLim, ZPainter, GRobinson, DSchieber, CThuring, JWong, LYin, MBurgess, ACatimel, BHawkins, PKtistakis, NStephens, LHolmes, ABThe 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. |
| spellingShingle | Conway, S Gardiner, J Grove, S Johns, M Lim, Z Painter, G Robinson, D Schieber, C Thuring, J Wong, L Yin, M Burgess, A Catimel, B Hawkins, P Ktistakis, N Stephens, L Holmes, AB Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title | Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title_full | Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title_fullStr | Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title_full_unstemmed | Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title_short | Synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes. |
| title_sort | synthesis and biological evaluation of phosphatidylinositol phosphate affinity probes |
| work_keys_str_mv | AT conways synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT gardinerj synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT groves synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT johnsm synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT limz synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT painterg synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT robinsond synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT schieberc synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT thuringj synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT wongl synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT yinm synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT burgessa synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT catimelb synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT hawkinsp synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT ktistakisn synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT stephensl synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes AT holmesab synthesisandbiologicalevaluationofphosphatidylinositolphosphateaffinityprobes |