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

被引：13

作者：

Chandler, Brent D. ^{[1
]}

Burkhardt, Anne L. ^{[2
]}

Foley, Klaudia ^{[2
]}

Cullis, Courtney ^{[2
]}

Driscoll, Denise ^{[2
]}

D'Amore, Natalie Roy ^{[2
]}

Miller, Scott J. ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Takeda Pharmaceut Int Co, Discovery, Cambridge, MA 02139 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 01期

关键词：

MONOCLONAL-ANTIBODIES; PHOSPHORYLATION; CATALYSIS; PHOSPHOINOSITIDES; 3-PHOSPHATE; CONJUGATION; DERIVATIVES; PROTEINS; INSIGHTS;

D O I：

10.1021/ja410750a

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：412 / 418

页数：7

共 42 条

[1] Atsuo M., 1988, MOL IMMUNOL, V25, P1025
[2] Phosphoinositide Signaling: New Tools and Insights
Balla, Tamas
Szentpetery, Zsofia
Kim, Yeun Ju
[J]. PHYSIOLOGY, 2009, 24 (04) : 231 - 244
[3] A SIMPLE AND EFFECTIVE CHEMICAL PHOSPHORYLATION PROCEDURE FOR BIOMOLECULES
BANNWARTH, W
TRZECIAK, A
[J]. HELVETICA CHIMICA ACTA, 1987, 70 (01) : 175 - 186
[4] Sulfhydryl-based tumor antigen-carrier protein conjugates stimulate superior antitumor immunity against B cell lymphomas
Betting, David J.
Kafi, Kamran
Abdollahi-Fard, Alireza
Hurvitz, Sara A.
Timmerman, John M.
[J]. JOURNAL OF IMMUNOLOGY, 2008, 181 (06) : 4131 - 4140
[5] THE TOTAL SYNTHESIS OF MYOINOSITOL PHOSPHATES VIA MYOINOSITOL ORTHOFORMATE
BILLINGTON, DC
BAKER, R
KULAGOWSKI, JJ
MAWER, IM
VACCA, JP
DESOLMS, SJ
HUFF, JR
[J]. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1989, (08): : 1423 - 1429
[6] GENERAL-SYNTHESIS OF PHOSPHATIDYLINOSITOL 3-PHOSPHATES
BRUZIK, KS
KUBIAK, RJ
[J]. TETRAHEDRON LETTERS, 1995, 36 (14) : 2415 - 2418
[7] Chemical Modification of Proteins at Cysteine: Opportunities in Chemistry and Biology
Chalker, Justin M.
Bernardes, Goncalo J. L.
Lin, Yuya A.
Davis, Benjamin G.
[J]. CHEMISTRY-AN ASIAN JOURNAL, 2009, 4 (05) : 630 - 640
[8] Synthesis of photoactivatable 1,2-O-diacyl-sn-glycerol derivatives of 1-L-phosphatidyl-D-myo-inositol 4,5-bisphosphate (PtdInsP(2)) and 3,4,5-trisphosphate (PtdInsP(3))
Chen, J
Profit, AA
Prestwich, GD
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (18) : 6305 - 6312
[9] Asymmetric total synthesis of phosphatidylinositol 3-phosphate and 4-phosphate derivatives
Chen, J
Feng, L
Prestwich, GD
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (19) : 6511 - 6522
[10] A monoclonal antibody to visualize Ptdlns(3,4,5)P3 in cells
Chen, RY
Kang, VH
Chen, J
Shope, JC
Torabinejad, J
DeWald, DB
Prestwich, GD
[J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2002, 50 (05) : 697 - 708

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