DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF HIGH-AFFINITY FKBP LIGANDS AND THE X-RAY CRYSTAL-STRUCTURES OF THEIR COMPLEXES WITH FKBP12

被引：198

作者：

HOLT, DA

LUENGO, JI

YAMASHITA, DS

OH, HJ

KONIALIAN, AL

YEN, HK

ROZAMUS, LW

BRANDT, M

BOSSARD, MJ

LEVY, MA

EGGLESTON, DS

LIANG, J

SCHULTZ, LW

STOUT, TJ

CLARDY, J

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT PHYS & STRUCT CHEM,KING OF PRUSSIA,PA 19406

[2] CORNELL UNIV,DEPT CHEM,ITHACA,NY 14853

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 1993年 / 115卷 / 22期

关键词：

D O I：

10.1021/ja00075a008

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The design and synthesis of high-affinity FKBP12 ligands is described. These compounds potently inhibit the cis-trans-peptidylprolyl isomerase (rotamase) activity catalyzed by FKBP12 with inhibition constants (K(i,app)) as low as 1 nM, yet they possess remarkable structural simplicity relative to FK506 and rapamycin, from which they are conceptually derived. The atomic structures of three FKBP12-ligand complexes and of one unbound ligand were determined by X-ray crystallography and are compared to the FKBP12-FK506 and FKBP12-rapamycin complexes.

引用

页码：9925 / 9938

页数：14

共 67 条

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