Selective mode of action of guanidine-containing non-peptides at human NPFF receptors
Findeisen, Maria ; Würker, Cäcilia ; Rathmann, Daniel ; Meier, René ; Meiler, Jens ; Olsson, Roger LU
and Beck-Sickinger, Annette G.
(2012)
In Journal of Medicinal Chemistry
55(13).
p.6124-6136
- Abstract
The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By use of four nonpeptidic compounds and the peptide mimetics RF9 and BIBP3226, agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated. The binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of... (More)
The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By use of four nonpeptidic compounds and the peptide mimetics RF9 and BIBP3226, agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated. The binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of AC-216 interacts with position 7.35 in the NPFF 1 but not in the NPFF 2 receptor. These results provide distinct insights into the receptor specific binding pockets, which is necessary for the development of drugs to address the NPFF system.
(Less)
- author
- Findeisen, Maria
; Würker, Cäcilia
; Rathmann, Daniel
; Meier, René
; Meiler, Jens
; Olsson, Roger
LU
and Beck-Sickinger, Annette G.
- publishing date
- 2012-07-12
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Medicinal Chemistry
- volume
- 55
- issue
- 13
- pages
- 6124 - 6136
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:22708927
- scopus:84863853873
- ISSN
- 0022-2623
- DOI
- 10.1021/jm300535s
- language
- English
- LU publication?
- no
- id
- 5723f8aa-af04-42da-aadf-342ad43bec81
- date added to LUP
- 2019-10-02 11:09:32
- date last changed
- 2024-04-02 19:15:36
@article{5723f8aa-af04-42da-aadf-342ad43bec81,
abstract = {{<p>The binding pocket of both NPFF receptors was investigated, focusing on subtype-selective behavior. By use of four nonpeptidic compounds and the peptide mimetics RF9 and BIBP3226, agonistic and antagonistic properties were characterized. A set of Ala receptor mutants was generated. The binding pocket was narrowed down to the upper part of transmembrane helices V, VI, VII and the extracellular loop 2. Positions 5.27 and 6.59 have been shown to have a strong impact on receptor activation and were suggested to form an acidic, negatively charged binding pocket in both NPFF receptor subtypes. Additionally, position 7.35 was identified to play an important role in functional selectivity. According to docking experiments, the aryl group of AC-216 interacts with position 7.35 in the NPFF <sub>1</sub> but not in the NPFF <sub>2</sub> receptor. These results provide distinct insights into the receptor specific binding pockets, which is necessary for the development of drugs to address the NPFF system.</p>}},
author = {{Findeisen, Maria and Würker, Cäcilia and Rathmann, Daniel and Meier, René and Meiler, Jens and Olsson, Roger and Beck-Sickinger, Annette G.}},
issn = {{0022-2623}},
language = {{eng}},
month = {{07}},
number = {{13}},
pages = {{6124--6136}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Medicinal Chemistry}},
title = {{Selective mode of action of guanidine-containing non-peptides at human NPFF receptors}},
url = {{http://dx.doi.org/10.1021/jm300535s}},
doi = {{10.1021/jm300535s}},
volume = {{55}},
year = {{2012}},
}