DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF HIGH-AFFINITY FKBP LIGANDS AND THE X-RAY CRYSTAL-STRUCTURES OF THEIR COMPLEXES WITH FKBP12
DESIGN, SYNTHESIS, AND KINETIC EVALUATION OF HIGH-AFFINITY FKBP LIGANDS AND THE X-RAY CRYSTAL-STRUCTURES OF THEIR COMPLEXES WITH FKBP12
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DOI：
10.1021/ja00075a008
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发表时间：
1993-11-03
影响因子：
15
通讯作者：
CLARDY, J
中科院分区：
文献类型：
--
作者：
HOLT, DA;LUENGO, JI;CLARDY, J
介绍了高亲和力FKBP12配体的设计和合成。这些化合物能有效地抑制FKBP12催化的顺式-反式氨基丙酰异构酶(Roamamase)的活性，抑制常数K(I，APP)低至1 nM，但相对于概念上衍生的FK506和雷帕霉素，它们具有显著的结构简单性。用X-射线单晶衍射法测定了三个FKBP12-配体络合物和一个非结合配体的原子结构，并与FKBP12-FK506和FKBP12-雷帕霉素络合物进行了比较。
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.