Details

Autor(en) / Beteiligte

• Young, Rodney C
• Downes, C. Peter
• Eggleston, Drake S
• Jones, Martin
• Macphee, Colin H
• Rana, Kishore K
• Ward, John G

Titel

Total synthesis of the four stereoisomers of dihexadecanoyl phosphatidylinositol and the substrate stereospecificity of human erythrocyte membrane phosphatidylinositol 4-kinase

Ist Teil von

• Journal of medicinal chemistry, 1990-02, Vol.33 (2), p.641-646

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1990

Quelle

MEDLINE

Beschreibungen/Notizen

• A new and convenient method for the preparation of the four stereoisomers of dihexadecanoyl phosphatidylinositol has been developed. An enantiomeric pair of acid-labile, pentaprotected myo-inositol building blocks was synthesized in high yield and coupled with chiral phenyl dihexadecanoylglyceryl phosphates to give the fully protected phosphatidylinositols. These were subsequently deprotected by hydrogenolysis and self-hydrolysis in aqueous ethanol to give the desired pure products. Comparison of these compounds as potential substrates for a partially purified phosphatidylinositol 4-kinase (EC 2.7.1.67) derived from human erythrocyte membranes revealed that the chirality of the inositol ring is crucial for efficient phosphorylation, whereas the chirality of the glycerol moiety is relatively unimportant. Moreover, the similarity in phosphorylation rates of the naturally occurring mammalian phospholipid, I, and its synthetic stereochemical counterpart, compound 10a, suggests that the enzyme is relatively tolerant to changes in fatty acid composition.