Photochromic peptidic NPY Y4 receptor ligandsElectronic supplementary information (ESI) available. See DOI: 10.1039/c8ob03221a

• Main Authors: Lachmann, D, Konieczny, A, Keller, M, König, B
• Format: Journal Article
• Language: English
• Published: 27.02.2019
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob03221a

The neuropeptide Y (NPY) Y 4 receptor is a G protein coupled receptor, which is targeted by pancreatic polypeptide, a homologue of NPY. Selective Y 4 R agonists were suggested as potential therapeutics for the treatment of obesity. Highly potent dimeric peptidic Y 4 R agonists, constituting two pentapeptide moieties connected through an aliphatic linker, represent an interesting class of Y 4 R ligands. Based on this compound class, photoresponsive Y 4 R ligands, containing an azobenzene, azopyrazole, diethienylethene or a fulgimide chromophore were prepared to explore structural requirements of such Y 4 R agonists on Y 4 R binding. The synthesized Y 4 R ligands, containing a non-aliphatic rigid photochromic linker, switch reversibly in aqueous buffer and exhibited high Y 4 R 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 Y 4 R binding. Differences in Y 4 R 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. Photoresponsive NPY Y 4 R ligands, containing an azobenzene, azopyrazole, diethienylethene or a fulgimide chromophore were prepared to explore structural requirements of Y 4 R agonists on Y 4 R binding.