A Fully Synthetic and Biochemically Validated Phosphatidyl Inositol-3-Phosphate Hapten via Asymmetric Synthesis and Native Chemical Ligation

作者：Chandler Brent D; Burkhardt Anne L; Foley Klaudia; Cullis Courtney; Driscoll Denise; D'Amore Natalie Roy; Miller Scott J^*

来源：Journal of the American Chemical Society, 2014, 136(1): 412-418.

DOI：10.1021/ja410750a

We report the synthesis and biochemical validation of a phosphatidyl inositol-3 phosphate (PI3P) immunogen. The inositol stereochemistry was secured through peptide-catalyzed asymmetric phosphorylation catalysis, and the subsequent incorporation of a cysteine residue was achieved by native chemical ligation (NCL). Conjugation of the PI3P hapten to maleimide-activated keyhole limpet hemocyanin (KLH) provided a PI3P immunogen, which was successfully used to generate selective PI3P antibodies. The incorporation of a sulfhydryl nucleophile into a phosphoinositide hapten demonstrates a general strategy to reliably access phosphoinositide immunogens.

• 出版日期2014-1-8