通过不对称合成和天然化学连接，全合成且经过生物化学验证的磷脂酰肌醇-3-磷酸半抗原。
A fully synthetic and biochemically validated phosphatidyl inositol-3-phosphate hapten via asymmetric synthesis and native chemical ligation.
机构信息
Department of Chemistry, Yale University , P.O. Box 208107, United States.
出版信息
J Am Chem Soc. 2014 Jan 8;136(1):412-8. doi: 10.1021/ja410750a. Epub 2013 Dec 17.
Abstract
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.
摘要
我们报告了一种磷酸肌醇-3 磷酸（PI3P）免疫原的合成和生化验证。通过肽催化的不对称磷酸化催化来确保肌醇立体化学，并且通过天然化学连接（NCL）实现了随后的半胱氨酸残基的掺入。PI3P 半抗原与马来酰亚胺活化的贻贝血红蛋白（KLH）的缀合提供了 PI3P 免疫原，该免疫原成功地用于生成选择性 PI3P 抗体。将巯基亲核试剂掺入磷酸肌醇化物半抗原中证明了一种可靠地获得磷酸肌醇化物免疫原的通用策略。
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