The nonapeptide hormone oxytocin (OT) has pivotal brain roles in social recognition and interaction and is thus a promising therapeutic drug for social deficits. Because of its peptide structure, however, OT is rapidly eliminated from the bloodstream, which decreases its potential therapeutic effects in the brain. We found that newly synthesized OT analogues in which the Pro of OT was replaced with N-( p-fluorobenzyl)glycine (2) or N-(3-hydroxypropyl)glycine (5) exhibited highly potent binding affinities for OT receptors and Ca mobilization effects by selectively activating OT receptors over vasopressin receptors in HEK cells, where 2 was identified as a superagonist ( E = 131%) for OT receptors. Furthermore, the two OT analogues had a remarkably long-acting effect, up to 16-24 h, on recovery from impaired social behaviors in two strains of CD38 knockout mice that exhibit autism spectrum disorder-like social behavioral deficits, whereas the effect of OT itself rapidly diminished.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.8b01691 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In vitro susceptibility of 147 international clinical Mycobacterium abscessus isolates to epetraborole and comparators by broth microdilution.
J Antimicrob Chemother
December 2024
Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO, USA.
Background: Mycobacterium abscessus is a highly drug-resistant non-tuberculous mycobacterium (NTM) for which treatment is limited by the lack of active oral antimycobacterials and frequent adverse reactions. Epetraborole is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis, and has been shown to have anti-M. abscessus activity in preclinical studies.
View Article and Find Full Text PDFA3AR antagonism mitigates metabolic dysfunction-associated steatotic liver disease by exploiting monocyte-derived Kupffer cell necroptosis and inflammation resolution.
Metabolism
December 2024
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk, South Korea. Electronic address:
Background & Aims: Metabolic dysfunction-associated steatotic liver (MASLD) progression is driven by chronic inflammation and fibrosis, largely influenced by Kupffer cell (KC) dynamics, particularly replenishment of pro-inflammatory monocyte-derived KCs (MoKCs) due to increased death of embryo-derived KCs. Adenosine A3 receptor (A3AR) plays a key role in regulating metabolism and immune responses, making it a promising therapeutic target. This study aimed to investigate the impact of selective A3AR antagonism for regulation of replenished MoKCs, thereby improving MASLD.
View Article and Find Full Text PDFLonicera caerulea genome reveals molecular mechanisms of freezing tolerance and anthocyanin biosynthesis.
J Adv Res
December 2024
Key Laboratory of Saline-alkali Vegetation Ecology Restoration (Northeast Forestry University), Ministry of Education, Harbin 150040, China; College of Life Science, Northeast Forestry University, Harbin 150040, China. Electronic address:
Introduction: Lonicera caerulea L. (blue honeysuckle) is a noteworthy fleshy-fruited tree and a prominent medicinal plant, which possesses notable characteristics such as exceptional resilience to winter conditions and early maturation, and the richest source of functional anthocyanins, particularly cyanidin-3-glucoside. The molecular mechanisms responsible for its freezing tolerance and anthocyanin biosynthesis remain largely unknown.
View Article and Find Full Text PDFSynergistic two-step inhibition approach using a combination of trametinib and onvansertib in KRAS and TP53-mutated colorectal adenocarcinoma.
Biomed Pharmacother
December 2024
Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea. Electronic address:
Colorectal malignancies associated with KRAS and TP53 mutations led us to investigate the effects of combination therapy targeting KRAS, MEK1, or PLK1 in colorectal cancer. MEK1 is downstream of RAS in the MAPK pathway, whereas PLK1 is a mitotic kinase of the cell cycle activated by MAPK and regulated by p53. Bioinformatics analysis revealed that patients with colorectal cancer had a high expression of MAP2K1 and PLK1.
View Article and Find Full Text PDFTo realize the aim of easy and accurate detection of ammonia and picric acid (PA) in both aqueous and vapor phases based on function-oriented investigation principles, in the present study, we include a luminescent performance with recognition performance, taking into account the application conditions. Zn(II) ions with luminescence qualities and an amine-substituted imidazole moiety with selective recognition properties towards picric acid and ammonia are coupled to generate a novel 1D luminous Zn(II) coordination polymer, Zn-CP [{Zn(II)( 2-ABZ)2(2-BDC)}].MeOH]∞, where 2-ABZ and 2-BDC stand for terephthalic acid and protonated 2 aminobenzimidazole, respectively.
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!