Ulrich Sensfuss

Identification and in Vivo and in Vitro Characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) Selective α-Melanocyte-Stimulating Hormone (α-MSH) Analogues

We report in vitro and in vivo data of new α-melanocyte-stimulating hormone (α-MSH) analogues which are N-terminal modified with a long chain fatty acid derivative. While keeping the pharmacophoric motif (d-Phe-Arg-Trp) fixed, we tried to improve selectivity and physicochemical parameters like solubility and stability of these analogues by replacing amino acids further away from the motif. Receptor specific changes in binding affinity to the melanocortin receptors were observed between the acetyl derivatives and the fatty acid analogues. Furthermore, amino acids at the N-terminal of α-MSH (Ser-Tyr-Ser) not considered to be part of the pharmacophore were found to have an influence on the MC4/MC1 receptor selectivity. While the acetyl analogues have an in vivo effect for around 7 h, the long chain fatty acid analogues have an effect up to 48 h in an acute feeding study in male Sprague-Dawley rats after a single subcutaneous administration.

Solid-phase aldol condensations mediated by zinc acetate and 2,2′-bipyridine under weakly basic conditions

Abstract A new, efficient and convenient method for the synthesis of resin-bound α,β-unsaturated ketones is described. Reaction of polystyrene-linked benzaldehydes with methyl ketones or tetralone in the presence of zinc acetate, 2,2′-bipyridine and an amidine base at elevated temperature gave resin-bound (E)-enones in high purity. These were transformed into thioethers by reaction with thiophenol.