ArticleChemMedChem2014
Position and length of fatty acids strongly affect receptor selectivity pattern of human pancreatic polypeptide analogues.
Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- The pathway-independent positive allosteric modulator C1 allows for the identification of active YCellular and molecular life sciences : CMLS · 2026Article
- Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity.Molecular cancer therapeutics · 2024Article
- Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptide.Frontiers in pharmacology · 2024Article
- Dynamics of the Second Extracellular Loop Control Transducer Coupling of Peptide-Activated GPCRs.International journal of molecular sciences · 2023Article
- The effect of fatty diacid acylation of human PYYScientific reports · 2021Article
- Discovery and Characterization of VU0529331, a Synthetic Small-Molecule Activator of Homomeric G Protein-Gated, Inwardly Rectifying, Potassium (GIRK) Channels.ACS chemical neuroscience · 2019Article
- Structure-specific effects of lipidated oxytocin analogs on intracellular calcium levels, parental behavior, and oxytocin concentrations in the plasma and cerebrospinal fluid in mice.Pharmacology research & perspectives · 2017Article
- High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice.British journal of pharmacology · 2016Article
- Article
- Novel enzyme-resistant pancreatic polypeptide analogs evoke pancreatic beta-cell rest, enhance islet cell turnover, and inhibit food intake in mice.BioFactors (Oxford, England)Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.