RATIONAL DESIGN OF ORTHOGONAL RECEPTOR-LIGAND COMBINATIONS

被引：78

作者：

BELSHAW, PJ ^{[1
]}

SCHOEPFER, JG ^{[1
]}

LIU, KQ ^{[1
]}

MORRISON, KL ^{[1
]}

SCHREIBER, SL ^{[1
]}

机构：

[1] HARVARD UNIV,HOWARD HUGHES MED INST,DEPT CHEM,CAMBRIDGE,MA 02138

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH | 1995年 / 34卷 / 19期

关键词：

CYCLOPHILIN; CYCLOSPORINE; IMMUNOPHILINS; PROTEIN DIMERIZATION;

D O I：

10.1002/anie.199521291

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A novel approach to understanding protein–ligand interactions is illustrated using the immunophilin receptor human cyclophilin A and its immunosuppressive ligand cyclosporin A. Synthetic chemistry is used to place “bumps” on the ligand, while site‐directed mutagenesis is used to create compensatory “holes” in the receptor. These novel receptor–ligand combinations can have an affinity even greater than that of the natural system, and are expected to facilitate the inducible dimerization of target proteins, and thus the activation of signaling proteins, in transgenic animals. Copyright © 1995 by VCH Verlagsgesellschaft mbH, Germany

引用

页码：2129 / 2132

页数：4

共 23 条

[1]

Austin D J, 1994, Chem Biol, V1, P131, DOI 10.1016/1074-5521(94)90002-7

[2]

BELSHAW PJ, UNPUB CHEM BIOL

[3] EFFECT OF TERTIARY BASES ON O-BENZOTRIAZOLYLURONIUM SALT-INDUCED PEPTIDE SEGMENT COUPLING [J].

CARPINO, LA ;

EL-FAHAM, A .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (04) :695-698

[4] THE ROLE OF PROTEIN-TYROSINE KINASES AND PROTEIN-TYROSINE PHOSPHATASES IN T-CELL ANTIGEN RECEPTOR SIGNAL-TRANSDUCTION [J].

CHAN, AC ;

DESAI, DM ;

WEISS, A .

ANNUAL REVIEW OF IMMUNOLOGY, 1994, 12 :555-592

[5] A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE [J].

CLACKSON, T ;

WELLS, JA .

SCIENCE, 1995, 267 (5196) :383-386

[6] COUPLING N-METHYLATED AMINO-ACIDS USING PYBROP AND PYCLOP HALOGENOPHOSPHONIUM SALTS - MECHANISM AND FIELDS OF APPLICATION [J].

COSTE, J ;

FREROT, E ;

JOUIN, P .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (09) :2437-2446

[7] CYCLOPHILIN - A SPECIFIC CYTOSOLIC BINDING-PROTEIN FOR CYCLOSPORIN-A [J].

HANDSCHUMACHER, RE ;

HARDING, MW ;

RICE, J ;

DRUGGE, RJ .

SCIENCE, 1984, 226 (4674) :544-547

[8] COMPARATIVE BINDING-STUDIES OF CYCLOPHILINS TO CYCLOSPORINE-A AND DERIVATIVES BY FLUORESCENCE MEASUREMENTS [J].

HUSI, H ;

ZURINI, MGM .

ANALYTICAL BIOCHEMISTRY, 1994, 222 (01) :251-255

[9]

IRELAND RE, 1979, TETRAHEDRON LETT, P4705

[10] CRYSTAL-STRUCTURES OF CYCLOPHILIN-A COMPLEXED WITH CYCLOSPORINE-A AND N-METHYL-4-[(E)-2-BUTENYL]-4,4-DIMETHYLTHREONINE CYCLOSPORINE-A [J].

KE, HM ;

MAYROSE, D ;

BELSHAW, PJ ;

ALBERG, DG ;

SCHREIBER, SL ;

CHANG, ZY ;

ETZKORN, FA ;

HO, S ;

WALSH, CT .

STRUCTURE, 1994, 2 (01) :33-44

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