Stereospecific synthesis of a carbene-generating angiotensin II analogue for comparative photoaffinity labeling: improved incorporation and absence of methionine selectivity
| Autor: | Dany Fillion, Emanuel Escher, Brian J. Holleran, Maud Deraët |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Stereochemistry Phenylalanine Convergent synthesis Photoaffinity Labels Chemical synthesis Receptor Angiotensin Type 2 Iodine Radioisotopes chemistry.chemical_compound Radioligand Assay Structure-Activity Relationship Methionine Drug Discovery Chlorocebus aethiops Animals Humans Receptor Photoaffinity labeling Angiotensin II Stereoisomerism Ligand (biochemistry) Hydrocarbons chemistry Diazomethane Isotope Labeling Diazirine COS Cells Mutation Molecular Medicine Methane hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of medicinal chemistry. 49(7) |
| ISSN: | 0022-2623 |
| Popis: | A stereospecific convergent synthesis of N-[(9-fluorenyl)methoxycarbonyl]-p-[3-(trifluoromethyl)-3H-diazirin-3-yl]-l-phenylalanine (Fmoc-12, Fmoc-Tdf) and its incorporation into the C-terminal position of the angiotensin II (AngII) peptide to form (125)I[Sar(1),Tdf(8)]AngII ((125)I-13) is presented. This amino acid photoprobe is a highly reactive carbene-generating diazirine phenylalanine derivative that can be used for photoaffinity labeling. Using model receptors, we compared the reactivity and the Met selectivity of 12 to that of the widely used and reputedly Met-selective p-benzoyl-l-phenylalanine (Bpa) photoprobe. Wild-type and mutant AngII type 2 receptors, a G protein-coupled receptors, were photolabeled with (125)I-13 as well as with (125)I[Sar(1),Bpa(8)]AngII ((125)I-14), and the respective incorporation yields were assessed. The carbene-generating 12 was more reactive toward inert residues and was not Met-selective compared to the biradical ketone-generating Bpa, allowing for more precise determination of ligand contact points in peptidergic receptors. |
| Databáze: | OpenAIRE |
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