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Updated: Apr 25, 2026

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Position and length of fatty acids strongly affect receptor selectivity pattern of human pancreatic polypeptide
Veronika Mäde1, Kathrin Bellmann-Sickert, Anette Kaiser
1Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, Brüderstraße 34, 04103 Leipzig (Germany), Fax: (+49) 341-97-36909.
Abstract:
Pancreatic polypeptide (PP) is a satiety-inducing gut hormone targeting predominantly the Y4 receptor within the neuropeptide Y multiligand/multireceptor family. Palmitoylated PP-based ligands have already been reported to exert prolonged satiety-inducing effects in animal models. Here, we suggest that other lipidation sites and different fatty acid chain lengths may affect receptor selectivity and metabolic stability. Activity tests revealed significantly enhanced potency of long fatty acid conjugates on all four Y receptors with a preference of position 22 over 30 at Y1 , Y2 and Y5 receptors. Improved Y receptor selectivity was observed for two short fatty acid analogues. Moreover, [K(30)(E-Prop)]hPP2-36 (15) displayed enhanced stability in blood plasma and liver homogenates. Thus, short chain lipidation of hPP at key residue 30 is a promising approach for anti-obesity therapy because of maintained selectivity and a sixfold increased plasma half-life.
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