Targeting FKBP isoforms with small-molecule ligands

被引：67

作者：

Blackburn, Elizabeth A. ^{[1
]}

Walkinshaw, Malcolm D. ^{[1
]}

机构：

[1] Univ Edinburgh, CTCB, ISMB, Edinburgh EH9 3JR, Midlothian, Scotland

来源：

CURRENT OPINION IN PHARMACOLOGY | 2011年 / 11卷 / 04期

关键词：

FK506; BINDING-PROTEINS; IMMUNOPHILINS; INHIBITORS; COMPLEXES; AFFINITY; DESIGN; IDENTIFICATION; DENATURATION; DISCOVERY; SEQUENCE;

D O I：

10.1016/j.coph.2011.04.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The FK506 binding protein (FKBP) family of proteins provide an interesting series of drug targets since different isoforms modulate diverse cellular pathways. There are therapeutic opportunities in the fields of cancer therapy, neurodegenerative conditions and psychiatric disorders. X-ray crystallographic or NMR data are available for eight of fourteen human FKBPs covering ten of the twenty-two different FKBP domains. We have made a detailed sequence and structural comparison of human FKBP domains. These data show that the chemical scaffolds common to the immunosuppressive inhibitors FK506 and rapamycin bind to the most conserved region of the binding site. This observation opens the way to the design of isoform specific inhibitors.

引用

页码：365 / 371

页数：7

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