Efficient semisynthesis of a tetraphosphorylated analogue of the type I TGFβ receptor

被引：50

作者：

Flavell, RR

Huse, M

Goger, M

Trester-Zedlitz, M

Kuriyan, J

Muir, TW

机构：

[1] Rockefeller Univ, Lab Synthet Prot Chem, New York, NY 10021 USA

[2] Rockefeller Univ, Mol Biophys Lab, New York, NY 10021 USA

来源：

ORGANIC LETTERS | 2002年 / 4卷 / 02期

关键词：

D O I：

10.1021/ol016859i

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Semisynthesis of an active tetra phosphorylated analogue of the Type I TGFbeta receptor is reported. An efficient native chemical ligation protocol was developed to link a tetraphosphopeptide and a recombinant receptor fragment. Synthesis of the peptide alpha-thioester on a 4-sulfamylbutyryl resin was optimized following the characterization of a major side reaction and subsequent substitution of norleucine for methionine in the peptide sequence. These optimized protocols will be applicable to the semisynthesis of related protein kinases.

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页码：165 / 168

页数：4

相关论文

共 18 条

[1] Backbone amide linker (BAL) strategy for Nα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of unprotected peptide p-nitroanilides and thioesters [J].

Alsina, J ;

Yokum, TS ;

Albericio, F ;

Barany, G .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (24) :8761-8769

[2] Activation method to prepare a highly reactive acylsulfonamide ''safety-catch'' linker for solid-phase synthesis [J].

Backes, BJ ;

Virgilio, AA ;

Ellman, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (12) :3055-3056

[3] An alkanesulfonamide "safety-catch" linker for solid-phase synthesis [J].

Backes, BJ ;

Ellman, JA .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (07) :2322-2330

[4] A GENERAL-METHOD FOR THE SYNTHESIS OF THIOESTER RESIN LINKERS FOR USE IN THE SOLID-PHASE SYNTHESIS OF PEPTIDE-ALPHA-THIOACIDS [J].

CANNE, LE ;

WALKER, SM ;

KENT, SBH .

TETRAHEDRON LETTERS, 1995, 36 (08) :1217-1220

[5]

Clippingdale AB, 2000, J PEPT SCI, V6, P225, DOI 10.1002/(SICI)1099-1387(200005)6:5<225::AID-PSC244>3.3.CO

[6]

2-K

[7] SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION [J].

DAWSON, PE ;

MUIR, TW ;

CLARKLEWIS, I ;

KENT, SBH .

SCIENCE, 1994, 266 (5186) :776-779

[8] Preparation of peptide thioesters using Fmoc-solid-phase peptide synthesis and its application to the construction of a template-assembled synthetic protein (TASP) [J].

Futaki, S ;

Sogawa, K ;

Maruyama, J ;

Asahara, T ;

Niwa, M ;

Hojo, H .

TETRAHEDRON LETTERS, 1997, 38 (35) :6237-6240

[9] Semisynthesis of hyperphosphorylated type I TGFβ receptor:: Addressing the mechanism of kinase activation [J].

Huse, M ;

Holford, MN ;

Kuriyan, J ;

Muir, TW .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (34) :8337-8338

[10] The TGFβ receptor activation process:: An inhibitor- to substrate-binding switch [J].

Huse, M ;

Muir, TW ;

Xu, L ;

Chen, YG ;

Kuriyan, J ;

Massagué, J .

MOLECULAR CELL, 2001, 8 (03) :671-682