Preparation of an unprotected phosphotyrosine building block and its application in solid-phase synthesis of phosphopeptides

A new and facile synthesis of tyrosine phosphorylated peptides has been developed. ^N-Fmoc-Tyr^tBu)-OPfp was treated with TFA, phosphorylated with phosphorous oxychloride and the resulting phosphoric acid dichloride was hydrolysed to give N-Fmoc-Tyr(PO₃H₃2)-OPfp 1 in an overall yield of 98%. Compound 1 was used in solid-phase peptide synthesis of phosphopeptides 2, 3 and 4, which are fragments of murine adipocyte lipid binding protein. The advantage of using the Pfp ester was the absence of pyrophosphates and other byproducts.     

Syntheses and antiproliferative evaluation of oxyphenisatin derivatives

Syntheses and structure-antiproliferative relationship for oxyphenisatin analogues are described. The cell proliferation data showed that the presence of substituents (especially F, Cl, Me, CF(3), and OMe) in the 6- and 7-position of oxyphenisatin markedly enhanced the potency in the MDA-468 cell line without affecting the MDA-231 cell line. The best compounds from this series showed low nanomolar antiproliferative activity towards the MDA-468 cell line and a 1000-fold selectivity over the MDA-231 cell line.     

Preparation of an unprotected phosphotyrosine building block and its application in solid-phase synthesis of phosphopeptides

Summary A new and facile synthesis of tyrosine phosphorylated peptides has been developed.N ^α-Fmoc-Tyr(tBu)-OPfp was treated with TFA, phosphorylated with phosphorous oxychloride and the resulting phosphoric acid dichloride was hydrolysed to giveN ^α-Fmoc-Tyr(PO₃H₂)-OPfp1 in an overall yield of 98%. Compound1 was used in solid-phase peptide synthesis of phosphopeptides2, 3 and4, which are fragments of murine adipocyte lipid binding protein. The advantage of using the Pfp ester was the absence of pyrophosphates and other byproducts.