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Synthesis and biological evaluation of new dual APN/NEP inhibitors as potent analgesics.
Bioorg Chem
January 2025
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address:
An alternative approach for the management of acute and chronic pains involves prolonging the half-life of endogenous opiates, such as enkephalins that are released in response to nociceptive stimuli. This can be achieved through the inhibition of enzymatic pathways responsible for the hydrolysis of these peptides, particularly targeting Aminopeptidase N (APN) and Neutral Endopeptidase (NEP). In this study, we designed and synthesized a series of dual enkephalinase inhibitors (DENKIs) targeting both APN and NEP as novel analgesic treatments.
View Article and Find Full Text PDFThe Role of Endogenous Beta-Endorphin and Enkephalins in the Crosstalk Between Ethanol and Morphine.
Pharmaceuticals (Basel)
January 2025
Department of Biotechnology and Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol, by causing the release of opioid peptides, may sensitize the system to the action of exogenous opioids such as morphine.
View Article and Find Full Text PDFA Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System.
Biomedicines
January 2025
Program of Immunology and Immunotherapy, CIMA-Universidad de Navarra, 31008 Pamplona, Spain.
Fibromyalgia represents a chronic pain disorder characterized by musculoskeletal pain, fatigue, and cognitive impairments. The exact mechanisms underlying fibromyalgia remain undefined; as a result, diagnosis and treatment present considerable challenges. On the other hand, the endogenous opioid system is believed to regulate pain intensity and emotional responses; hence, it might be expected to play a key role in the enhanced sensitivity experienced by fibromyalgia patients.
View Article and Find Full Text PDFImpact of β-casein variants on the formation of β-casomorphins in blue cheeses: Investigating key drivers through peptidomic analysis.
Food Res Int
February 2025
Department of Agriculture, University of Naples "Federico II", 80055 Portici, Italy.
β-Casomorphins (BCMs), food-associated peptides resulting from the proteolytic cleavage of β-casein (β-CN), have been widely investigated for their opioid-like activity. This research aimed to identify the presence of BCM7, BCM6, and BCM5 in different bovine milk-deriving blue cheese types and to describe the intricate mechanisms behind their formation, focusing on their origin from cheese with β-CN A1 and A2 variants. Using nanoLC-ESI-Q-Orbitrap-MS/MS and advanced computational tools, we explored the peptidomes of Bleu d'Auvergne, Gorgonzola, Stilton, and Bergader blue cheeses from milk containing both β-CN A1 and A2 variants.
View Article and Find Full Text PDFLower Diversity of Amylase-Trypsin Inhibitors and -Released Opioid-Containing Peptides in Ancestral Compared to Modern Wheat Varieties Assessed by Proteomics and Peptidomics.
J Agric Food Chem
January 2025
Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1433 Ås, Norway.
This study focused on identifying amylase-trypsin inhibitors (ATIs) in seven Norwegian-cultivated wheat varieties, including common wheat and ancestral species, and identifying potentially harmful opioid peptides within the digesta of these wheats. LC-MS/MS analysis of tryptic peptides from ATI fractions revealed that the common wheat variety Børsum exhibited the highest diversity of ATIs ( = 24), while they were less represented in tetraploid emmer ( = 11). Hexaploid wheat Bastian showed low diversity and relative abundance of ATIs.
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