Replacement of Thr32 and Gln34 in the C-terminal neuropeptide Y fragment 25-36 by cis-cyclobutane- and cis-cyclopentane β-amino acids shifts selectivity toward the Y4 receptor

Neuropeptide Y (NPY) and pancreatic polypeptide (PP) control central and peripheral processes by activating the G protein coupled receptors YxR (x = 1,2,4,5). We present analogs of the C-terminal fragments 25-36 and 32-36 of NPY and PP containing (1R,2S)-cyclobutane (βCbu) or (1R,2S)-cyclopentane (βCpe), which display exclusively Y4R affinity. In particular, [βCpe34]-NPY-(25-36) is a Y4R selective partial agonist (EC50 41±6 nM, Emax 71%), which binds Y4R with a Ki of 10±2 nM and a selectivity >100-fold relative to Y1R and Y2R, and >50-fold relative to Y5R. Comparably, [Y32, βCpe34]-NPY(PP)-(32-36) selectively binds and activates Y4R (EC50 94±21 nM, Emax 73%). The NMR structure of [βCpe34]-NPY-(25-36) in dodecylphosphatidylcholine micelles shows a short helix at residues 27-32, while the C-terminal segment R33βCpe34R35Y36 is extended. The biological properties of the βCbu- or βCpe-containing NPY and PP C-terminal fragments encourage the future application of these cyclic β-amino acids in the synthesis of selective Y4R ligands

Replacement of Thr³² and Gln³⁴ in the <i>C</i>‑Terminal Neuropeptide Y Fragment 25–36 by <i>cis</i>-Cyclobutane and <i>cis</i>-Cyclopentane β‑Amino Acids Shifts Selectivity toward the Y₄ Receptor

Neuropeptide Y (NPY) and pancreatic polypeptide (PP) control central and peripheral processes by activating the G protein coupled receptors Y_<i>x</i>R (<i>x</i> = 1, 2, 4, 5). We present analogs of the <i>C</i>-terminal fragments 25–36 and 32–36 of NPY and PP containing (1<i>R</i>,2<i>S</i>)-cyclobutane (βCbu) or (1<i>R</i>,2<i>S</i>)-cyclopentane (βCpe) β-amino acids, which display exclusively Y₄R affinity. In particular, [βCpe³⁴]-NPY-(25–36) is a Y₄R selective partial agonist (EC₅₀ 41 ± 6 nM, <i>E</i>_max 71%) that binds Y₄R with a <i>K</i>_i of 10 ± 2 nM and a selectivity >100-fold relative to Y₁R and Y₂R and >50-fold relative to Y₅R. Comparably, [Y³², βCpe³⁴]-NPY­(PP)-(32–36) selectively binds and activates Y₄R (EC₅₀ 94 ± 21 nM, <i>E</i>_max 73%). The NMR structure of [βCpe³⁴]-NPY-(25–36) in dodecylphosphatidylcholine micelles shows a short helix at residues 27–32, while the <i>C</i>-terminal segment R³³βCpe³⁴R³⁵Y³⁶ is extended. The biological properties of the βCbu- or βCpe-containing NPY and PP <i>C</i>-terminal fragments encourage the future application of these β-amino acids in the synthesis of selective Y₄R ligands

The lowland stream monitoring dataset (KgM, Kleingewässer-Monitoring) 2018, 2019

Plant protection products in the environment are partly responsible for the progressive loss of biodiversity. The mostly insufficient ecological status of surface waters is often explained by habitat degradation and excessive nutrient input. But what role do plant protection products play in this context? The Kleingewässermonitoring (KgM) project provides a worldwide unique quantitative assessment of the impact of pesticides from diffuse agricultural sources on small and medium-sized streams. The dataset comprises 124 monitoring stream sections all over Germany covering a wide pollution gradient where consistent measurements were carried out in 2018 and 2019 during the major pesticide application period from April to July. These measurements include event-driven sampling to record surface rainfall-induced short-term peak concentrations in addition to regular grab sampling of pesticides and a wide range of other pollutants resulting in more than 1,000 water samples. All further relevant anthropogenic and environmental parameters reigning ecological stream quality were recorded comprehensively (morphological and stream bed structure, temperature, flow velocity, dissolved oxygen, pH, catchment land use, stream profile). The dataset also contains effect monitoring data featuring sampled invertebrate communities and bioassay analyses of water samples. The data enables an assessment of pesticide exposure and related effects as well as the analysis of complex causal relationships in streams