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

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• 作者：Brent D. Chandler ; Anne L. Burkhardt ; Klaudia Foley ; Courtney Cullis ; Denise Driscoll ; Natalie Roy D’Amore ; Scott J. Miller
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：January 8, 2014
• 年：2014
• 卷：136
• 期：1
• 页码：412-418
• 全文大小：368K
• ISSN：1520-5126

文摘

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.