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.
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页码：9925 / 9938
页数：14
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