The cross influence of polypeptides (substance P, eledoisin) and neurotransmitters (acetylcholine, histamine, 5-hydroxytryptamine, ATP) on isolated guinea pig ileum involved a reduction or loss of muscle sensitivity. After the desensitization induced by one of the neurotransmitters the sensitivity of the ileum longitudinal muscle to polypeptides as estimated by the dissociation constant of the drug-receptor complex, decreased, i.e. a non-specific cross desensitization occurred. 5-hydroxytrpyptamine, however, increased the sensitivity to the polypeptides. A similar sensibilizing effect is characteristic of the polypeptides which, after application, increased 1.5-2.0-fold the height of the maximum muscle contraction and decreased 2-4-fold the dissociation constant. A possible involvement of polypeptides not only in their interaction with the target cells but also in the modulation of neurotransmitters, is discussed.
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Proc Natl Acad Sci U S A
January 2025
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80305.
Immunological interventions, like vaccinations, are enabled by the predictive control of humoral responses to novel antigens. While the development trajectories for many broadly neutralizing antibodies (bnAbs) have been measured, it is less established how human subtype-specific antibodies develop from their precursors. In this work, we evaluated the retrospective development trajectories for eight anti-SARS-CoV-2 Spike human antibodies (Abs).
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
January 2025
Amity Institute of Biotechnology, Amity University, Kolkata, India. Electronic address:
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) covers a range of liver conditions marked by the buildup of fat, spanning from simple fatty liver to more advanced stages like metabolic dysfunction-associated steatohepatitis and cirrhosis.
Methods: Our in-depth analysis of PNPLA3_WT and mutants (I148M (MT1) and C15S (MT2)) provides insights into their structure-function dynamics in lipid metabolism, especially lipid droplet hydrolysis and ABHD5 binding. Employing molecular docking, binding affinity, MD analysis, dissociation constant, and MM/GBSA analysis, we delineated distinct binding characteristics between wild-type and mutants.
Nucleic Acids Res
January 2025
Department of Peptide Therapeutics, Genentech, South San Francisco, CA 94080, USA.
mRNA display is an effective tool to identify high-affinity macrocyclic binders for challenging protein targets. The success of an mRNA display selection is dependent on generating highly diverse libraries with trillions of peptides. While translation elongation can canonically accommodate the 61 proteinogenic triplet codons, translation initiation is restricted to the native start codon AUG.
View Article and Find Full Text PDFNPJ Biosens
January 2025
Department of Electrical Engineering, University of Victoria, Victoria, BC V8W 3P6 Canada.
The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.
View Article and Find Full Text PDFIran J Pharm Res
September 2024
Department of Anatomy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, The People's Republic of China.
Background: High mobility group box 1 (HMGB1) plays an essential role in various pathological conditions, including inflammation, fibrosis, autoimmune diseases, and carcinogenesis. The quantification of HMGB1 in body fluids holds promise for clinical applications.
Objectives: This study aimed to isolate high-affinity single-stranded DNA (ssDNA) aptamers that target HMGB1.
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