Ghrelin and Y2 receptors play a central role in appetite regulation inducing opposite effects. The Y2 receptor induces satiety, while the ghrelin receptor promotes hunger and weight gain. However, the food regulating system is tightly controlled by interconnected pathways where redundancies can lead to poor efficacy and drug tolerance when addressing a single molecule. We developed a multitarget strategy to synthesize dual peptides simultaneously inhibiting the ghrelin receptor and stimulating the Y2 receptor. Dual peptides showed dual activity in vitro, and one compound induced a slight diminution of food intake in a rodent model of obesity. In addition, stability studies in rats revealed different behaviors between the dual peptide and its corresponding monomers. The Y2 receptor agonist was unstable in blood, while the dual peptide showed an intermediate stability compared to that of the highly stable ghrelin receptor inverse agonist.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm501702q | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CAFs-released exosomal CREB1 promotes cell progression and immune evasion in thyroid cancer via the positive regulation of CCL20.
Autoimmunity
December 2025
Department of Thyroid Head and Neck Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Background: Exosomes derived from cancer-associated fibroblasts (CAFs) can affect tumor microenvironment (TME) of thyroid cancer (TC). The cAMP response element binding protein 1 (CREB1) acts as a transcription factor to participate in cancer development. Currently, we aimed to explore the molecular mechanism of exosome-associated CREB1 and C-C motif chemokine ligand 20 (CCL20) in TC.
View Article and Find Full Text PDFInvolvement of PRDX6 in the protective role of MANF in acute lung injury in rats.
Exp Lung Res
January 2025
Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear.
View Article and Find Full Text PDFAdditive Effects of Glutathione in Improving Antibiotic Efficacy in HIV- Co-Infection in the Central Nervous System: A Systematic Review.
Viruses
January 2025
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity and mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), and persistent inflammation. Glutathione (GSH) has the therapeutic potential to enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, and mitigating immune dysfunction.
View Article and Find Full Text PDFConserved Nuclear Localization Signal in NS2 Protein of Bombyx Mori Bidensovirus: A Potential Invertebrate ssDNA Virus Trait.
Viruses
January 2025
School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis.
View Article and Find Full Text PDFInhibition of Aβ Aggregation by Cholesterol-End-Modified PEG Vesicles and Micelles.
Pharmaceutics
December 2024
Department of Applied Chemistry, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
: This study aimed to design and evaluate Chol-PEG micelles and Chol-PEG vesicles as drug delivery system (DDS) carriers and inhibitors of amyloid-β (Aβ) aggregation, a key factor in Alzheimer's disease (AD). : The physical properties of Chol-PEG assemblies were characterized using dynamic light scattering (DLS), electrophoretic light scattering (ELS), and transmission electron microscopy (TEM). Inhibitory effects on Aβ aggregation were assessed via thioflavin T (ThT) assay, circular dichroism (CD) spectroscopy, and native polyacrylamide gel electrophoresis (native-PAGE).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!