Development of benzophenone-alkyne bifunctional sigma receptor ligands.
Chembiochem
; 13(15): 2277-89, 2012 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-23001760
ABSTRACT
Sigma (σ) receptors are unique non-opioid binding sites that are associated with a broad range of disease states. Sigma-2 receptors provide a promising target for diagnostic imaging and pharmacological interventions to curb tumor progression. Most recently, the progesterone receptor (PGRMC1, 25 kDa) has been shown to have σ2 receptor-like binding properties, thus highlighting the need to understand the biological function of an 18 kDa protein that exhibits σ2-like photoaffinity labeling (denoted here as σ2-18k) but the amino acid sequence of which is not known. In order to provide new tools for the study of the σ2-18k protein, we have developed bifunctional σ receptor ligands each bearing a benzophenone photo-crosslinking moiety and an alkyne group to which an azide-containing biotin affinity tag can be covalently attached through click chemistry after photo-crosslinking. Although several compounds showed favorable σ2 binding properties, the highest affinity (2 nM) and the greatest potency in blocking photolabeling of σ2-18k by a radioactive photoaffinity ligand was shown by compound 22. These benzophenone-alkyne σ receptor ligands might therefore be amenable for studying the σ2-18k protein through chemical biology approaches. To the best of our knowledge, these compounds represent the first reported benzophenone-containing clickable σ receptor ligands, which might potentially have broad applications based on the "plugging in" of various tags.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzofenonas
/
Receptores sigma
/
Alcinos
Limite:
Humans
Idioma:
En
Revista:
Chembiochem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos