Photochromic peptidic NPY Y4 receptor ligands
| Autor: | Burkhard König, Max Keller, Adam Konieczny, Daniel Lachmann |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Chemistry Stereochemistry Organic Chemistry Chromophore 010402 general chemistry Neuropeptide Y receptor 01 natural sciences Biochemistry Pentapeptide repeat 0104 chemical sciences chemistry.chemical_compound Photochromism Azobenzene Physical and Theoretical Chemistry Receptor Linker G protein-coupled receptor |
| Zdroj: | Organic & Biomolecular Chemistry. 17:2467-2478 |
| ISSN: | 1477-0539 1477-0520 |
| DOI: | 10.1039/c8ob03221a |
| Popis: | The neuropeptide Y (NPY) Y4 receptor is a G protein coupled receptor, which is targeted by pancreatic polypeptide, a homologue of NPY. Selective Y4R agonists were suggested as potential therapeutics for the treatment of obesity. Highly potent dimeric peptidic Y4R agonists, constituting two pentapeptide moieties connected through an aliphatic linker, represent an interesting class of Y4R ligands. Based on this compound class, photoresponsive Y4R ligands, containing an azobenzene, azopyrazole, diethienylethene or a fulgimide chromophore were prepared to explore structural requirements of such Y4R agonists on Y4R binding. The synthesized Y4R ligands, containing a non-aliphatic rigid photochromic linker, switch reversibly in aqueous buffer and exhibited high Y4R affinity throughout. This demonstrated that the replacement of the highly flexible aliphatic linker by a considerably less flexible photochromic linker was well tolerated with respect to Y4R binding. Differences in Y4R affinity and activity between the individual photoisomers (varying in spatial orientation and flexibility) were marginal suggesting that the linking element in the dimeric ligands is less critical for the adaptation of high-affinity binding modes at the receptor. |
| Databáze: | OpenAIRE |
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