Publications by authors named "P Magotti"
We recently described C18 fatty acid acylated peptides as a new class of potent long-lasting single-chain RXFP1 agonists that displayed relaxin-like activities in vivo. Early pharmacokinetics and toxicological studies of these stearic acid acylated peptides revealed a relevant oxidative metabolism occurring in dog and minipig, and also seen at a lower extent in monkey and rat. Mass spectrometry combined to NMR spectroscopy studies revealed that the oxidation occurred, unexpectedly, on the stearic acid chain at ω-1, ω-2 and ω-3 positions.
View Article and Find Full Text PDFInhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels . The article describes the design of analogues of ProTx-II that safely display systemic blocking of Na1.7, resulting in a latency of response to thermal stimuli in rodents.
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- Human relaxin-2 is a hormone important for mediating blood flow changes during pregnancy and has potential benefits in treating acute heart failure, but its clinical use is limited due to a short half-life and requirement for intravenous administration.
- Researchers developed long-acting relaxin peptide mimetics by modifying the B-chain of relaxin, leading to simpler and more potent peptide agonists for the relaxin receptor RXFP1.
- These new lipidated peptide agonists demonstrated high activity, better bioavailability when taken subcutaneously, and longer half-lives, making them promising candidates for wider therapeutic use.
N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.
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- Cancer immunotherapy depends on T cells invading tumors, but the endothelium creates a barrier.
- Researchers found that high doses of T cells can bypass this barrier, aided by local production of the complement protein C3 and the activation of C5a.
- Blocking C3 or its receptor (C5aR1) reduces T cell infiltration and tumor control, indicating that local complement activation is crucial for successful T cell homing and effective immunotherapy.