English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51

Gaali, S., Feng, X., Haehle, A., Sippel, C., Bracher, A., & Hausch, F. (2016). Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51. JOURNAL OF MEDICINAL CHEMISTRY, 59(6), 2410-2422. doi:10.1021/acs.jmedchem.5b01355.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6B6B-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-6B6C-D
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Gaali, Steffen1, Author
Feng, Xixi1, Author
Haehle, Andreas1, Author
Sippel, Claudia1, Author
Bracher, Andreas2, Author              
Hausch, Felix1, Author
Affiliations:
1external, ou_persistent22              
2Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              

Content

show
hide
Free keywords: FKBP51; LIGANDS; STRESS; DOMAIN; HSP90; INHIBITORS; SCAFFOLD; ANALOGS
 Abstract: The FK506-binding. protein 51 (FKBP51) is a key regulator of stress hormone receptors and an established risk factor for stress-related disorders. Drug development for FKBP51 has been impaired by the structurally similar but functionally opposing homologue FKBP52. High selectivity between FKBP51 and FKBP52 can be achieved by ligands that stabilize a recently discovered FKBP51-favoring conformation. However, drug-like parameters for these ligands remained unfavorable. In the present study, we replaced the potentially labile pipecolic ester group of previous FKBP51 ligands by various low molecular weight amides. This resulted in the first series of pipecolic acid amides, which had much lower molecular weights without affecting FKBP51 selectivity. We discovered a geminally substituted cyclopentyl amide as a preferred FKBP51-binding motif and elucidated its binding mode to provide a new lead structure for future drug optimization.

Details

show
hide
Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: JOURNAL OF MEDICINAL CHEMISTRY
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 1155 16TH ST, NW, WASHINGTON, DC 20036 USA : AMER CHEMICAL SOC
Pages: - Volume / Issue: 59 (6) Sequence Number: - Start / End Page: 2410 - 2422 Identifier: ISSN: 0022-2623