Nischan N, Kasper M-A, Mathew T, Hackenberger C P R
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany.
Org Biomol Chem. 2016 Aug 21;14(31):7500-8. doi: 10.1039/c6ob00843g. Epub 2016 Jul 18.
With this study we introduce new unsymmetrical phosphites to obtain lipidated peptide-conjugates starting from easily accessible azide-modified amino acid or peptide precursors. For this purpose, we investigated which substituents at alkyl phosphites lead to the highest formation of mono-alkylated phosphoramidate peptides. We found that phosphites containing one alkyl-chain and two picolyl or benzyl-substituents delivered alkyl phosphoramidate-conjugates in high yields, which also allowed a chemoselective lipidation of an unprotected azido polypeptide. Finally, monolipidated phosphoramidate peptides obtained by the unsymmetrical Staudinger phosphite reaction led to the formation of micelle-like structures and cellular uptake.
在本研究中，我们引入了新的不对称亚磷酸酯，以从易于获得的叠氮化物修饰的氨基酸或肽前体出发获得脂化肽缀合物。为此，我们研究了亚磷酸酯上的哪些取代基会导致单烷基化氨基磷酸酯肽的最高产率形成。我们发现，含有一条烷基链和两个吡啶甲基或苄基取代基的亚磷酸酯能高产率地提供烷基氨基磷酸酯缀合物，这也使得未保护的叠氮基多肽能够进行化学选择性脂化。最后，通过不对称施陶丁格亚磷酸酯反应获得的单脂化氨基磷酸酯肽导致形成胶束样结构并被细胞摄取。
