Neurotensin (NT) is a 13-amino acid neuropeptide found in the central nervous system and in the gastrointestinal tract. It is closely associated anatomically with dopaminergic and other neurotransmitter systems, and evidence supports a role for NT agonists in the treatment of various neuropsychiatric disorders. However, NT is readily degraded by peptidases, so there is much interest in the development of stable NT agonists, that can be injected systemically, cross the blood-brain barrier (BBB), yet retains the pharmacological characteristics of native NT for therapeutic use in the treatment of diseases such as schizophrenia, Parkinson's disease and addiction.
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http://dx.doi.org/10.1016/j.peptides.2005.12.018 | DOI Listing |
J Am Chem Soc
January 2025
Department of Chemistry, Queen's University, Kingston, ON K7L 3N6, Canada.
Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591).
View Article and Find Full Text PDFClin Transl Sci
February 2025
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Tramadol, the 41st most prescribed drug in the United States in 2021 is a prodrug activated by CYP2D6, which is highly polymorphic. Previous studies showed enzyme-inhibitor affinity varied between different CYP2D6 allelic variants with dextromethorphan and atomoxetine metabolism. However, no study has compared tramadol metabolism in different CYP2D6 alleles with different CYP2D6 inhibitors.
View Article and Find Full Text PDFAngiotensin-I converting enzyme (ACE) regulates the levels of disparate bioactive peptides, notably converting angiotensin-I to angiotensin-II and degrading amyloid beta. ACE is a heavily glycosylated dimer, containing 4 analogous catalytic sites, and exists in membrane bound and soluble (sACE) forms. ACE inhibition is a frontline, FDA-approved, therapy for cardiovascular diseases yet is associated with significant side effects, including higher rates of lung cancer.
View Article and Find Full Text PDFFood Chem X
January 2025
School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Various lipid and biopolymer-based nanocarriers have been developed to encapsulate food ingredients. The selection of nanocarrier type, preparation techniques, and loading methods should consider the compatibility of nutrient properties, nanocarrier composition, and product requirements. This review focuses on the loading methods for hydrophilic and hydrophobic substances, along with a detailed exploration of nanocarrier categorization, composition, and preparation methods.
View Article and Find Full Text PDFis the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2.
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