Emilia Oueis

Background and Purpose: Haemorphins are known to target G protein‐coupled receptors and their reduced serum levels were associated with diabetes and obesity. This is consistent with inhibitory action on dipeptidyl peptidase IV, controlling GLP‐1 levels. The modulation of the GLP‐1 receptor by haemorphins as a mechanism for regulating glucose homeostasis was investigated. Experimental Approach: The effect of LVV‐haemorphin 7 (LVV‐H7) on GLP‐1 receptor was assessed in human embryonic kidney (HEK293) and rat insulinoma (INS‐1 832/3) cells using bioluminescence resonance energy transfer, downstream signalling, cell viability, insulin synthesis experimental and computational ligand binding analysis. Key Results: LVV‐H7 has positive action on GLP‐1 receptor occurring with GLP‐1 but not orforglipron (LY3502970), indicating a peptide–peptide interaction, causing a left shift in GLP‐1's dose responses. LVV‐H7 also potentiated GLP‐1‐induced insulin expression and its protective effect against glucose‐induced cytotoxicity. Moreover, LVV‐H7 slightly reduced the GLP‐1's association kinetics with no impact on its binding properties. Molecular docking supported by functional analysis showed the existence of a putative ‘allosteric’ binding site at the junction between the helical and the extracellular domains (ECDs) and highlighted the critical role of Trp6 of LVV‐H7 and Ser31 ^ECD /Glu34 ^ECD /Arg299 ^ECL2 /Asp372 ^ECL3 /Arg380 ^ECL3/ ™ ⁷ of GLP‐1 receptor. This also demonstrated that active GLP‐1/GLP‐1 receptor complex is required for the positive action of LVV‐H7. Conclusions and Implications: LVV‐H7 is active on the GLP‐1 receptor‐mediated metabolic pathways in pancreatic β‐cells. This is consistent with reduced serum haemorphin levels in diabetes/obesity, suggesting implications in glucose homeostasis. This constitutes the first Class B GPCR modulated by haemorphins, illustrating the role of haemorphin‐GPCR axis in physiology/pathophysiology.

Herein we report the synthesis and characterisation of heteroleptic cationic Ir(III) complexes, [Ir(ppy) ₂ (PyTz‐ R )][PF ₆ ] and [Ir(ppy) ₂ (iQTz‐ R )][PF ₆ ], (ppy: 2‐phenylpyridine, PyTz: 2‐(1 H ‐tetrazol‐5‐yl)pyridine, iQTz: 1‐(1 H ‐tetrazol‐5‐yl)iso‐quinoline and R : ─CH ₃ , ─CHF ₂ , ─CH ₂ CF ₃ or ─CH ₂ Ph‐ p ‐CF ₃ ). The parent Ir(ppy) ₂ (PyTz) and Ir(ppy) ₂ (iQTz) complexes were converted to the cationic derivatives by regiospecific tetrazole quaternisation adopting “chemistry‐on‐a‐complex” and “ligand‐first” approaches. Structures were confirmed by NMR/FTIR spectroscopies, mass spectrometry, and single‐crystal X‐ray crystallography. DFT was used to probe electronic changes upon quaternisation. Absorption spectra were broadly similar across all complexes (strong UV bands with weaker 300–450 nm MLCT features), whereas cationisation markedly altered emission: the neutral complexes showed vibronically structured emission (iQTz red‐shifted vs PyTz), while all cationic derivatives displayed broad, structureless, further red‐shifted profiles. The bathochromic shift increased with the electron‐withdrawing strength of the R group (─CHF ₂ > ─CH ₂ CF ₃ > ─CH ₂ Ph‐ p ‐CF ₃ ≈ ─CH ₃ ). The photoluminescence quantum yields for the cationic complexes were determined to be in the range of 3.3‐11.2%. The thermal stability of the complexes was evaluated by thermogravimetric analysis. Finally, the cationic complexes were qualitatively assessed for potential antimicrobial activity against E. coli and S. aureus , with activity observed against S. aureus in well‐diffusion experiments.

A hybrid VR-mechanochemistry laboratory model modernizes undergraduate chemistry teaching while reducing waste, energy use, and access barriers. Graphical abstract image generated with BioRender.

Natural products remain vital sources of therapeutics, particularly anti-infectives, and members of the phylum Myxococcota constitute an especially rich reservoir for their discovery. Based on decades of microbiological efforts, we present 154 new Myxococcota genomes and propose a revised taxonomy expanding the number of described families from 11 to 28 and genera from 32 to 90. Comparison with an equivalent set from the prime source Actinomycetota shows that Myxococcota possess a comparable biosynthetic diversity, underscoring their promise for large-scale isolation and sequencing efforts. The vast untapped potential reflected in 2,387 uncharacterized gene cluster families is highlighted by genome mining efforts, yielding four validated compounds exhibiting novel chemistry, including myxolutamids and myxopentacins. We show that many Myxococcota-derived natural products, such as myxolutamid A and two new sorangicin derivatives, are conserved within taxonomic lineages. New described families thus bear high biosynthetic potential underpinning the importance of precise taxonomic classification guiding targeted drug discovery.

Saccharomyces cerevisiae was cultured under the influence of static magnetic fields (SMFs) to assess their impact on the biosynthesis of silver nanoparticles (AgNPs). Cell-free media derived from SMF-exposed cultures facilitated the formation of AgNPs, with a significant reduction in nanoparticle size observed at an optimal field strength of 7 mT. AgNPs synthesized under SMF conditions exhibited smaller crystalline structures than those produced in control media, as evidenced by dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. Over a 75-day period, SMF-exposed AgNPs demonstrated enhanced stability, as determined by DLS and polydispersity index (PDI) assessments. Further analysis through sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR) suggested the formation of a protein corona on the AgNPs in SMF-treated samples, which likely inhibits agglomeration and enhances long-term stability. These findings indicate that SMF-induced stress in S. cerevisiae triggers the secretion of specific proteins that contribute to the stabilization of AgNPs, providing a novel approach to controlling nanoparticle synthesis and stability through magnetic field exposure.

The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide LM6 with the sequence LSKISGGIGPLVIPV-NH₂ and its cyclic derivatives LM13a and LM13b showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.

In recent years, the interest to develop cyclizations promoted by visible light has been gaining a lot of attention due to its sustainability aspect. In this review, we summarize the most important advances in this period by describing the methods used to generate different ring sizes, while focusing on the mechanistic details of these reactions.

Eine neue Substanzfamilie von ungewöhnlichen Sesquarterpenoiden (Persicamidine A–E) mit hoher antiviraler Aktivität wurde aus einem kürzlich entdeckten Aktinobakterien‐Stamm (Kibdelosporangium persicum sp. nov.) isoliert, welcher aus einem Wüstenhabitat im Iran stammt. Umfangreiche NMR‐Analysen entlarvten ein hexazyklisches Terpenoidmolekül mit einer modifizierten Zuckereinheit auf einer Seite und einer höchst ungewöhnlichen Isoharnstoffeinheit, die mit der Terpenoidstruktur verbunden ist. Die Strukturen der fünf Derivate unterschieden sich ausschließlich durch die Aminoalkyl‐Seitenkette, die an die Isoharnstoffeinheit gebunden ist. Die Persicamidine A–E zeigten eine starke Aktivität gegen hCoV‐229E‐ und SARS‐CoV‐2‐Viren im nanomolaren Bereich bei gleichzeitig sehr guten Selektivitätsindizes. Dies macht die Persicamidine zu vielversprechenden Ausgangsverbindungen für die Arzneimittelentwicklung.

A new family of highly unusual sesquarterpenoids (persicamidines A–E) exhibiting significant antiviral activity was isolated from a newly discovered actinobacterial strain, Kibdelosporangium persicum sp. nov., collected from a hot desert in Iran. Extensive NMR analysis unraveled a hexacyclic terpenoid molecule with a modified sugar moiety on one side and a highly unusual isourea moiety fused to the terpenoid structure. The structures of the five analogues differed only in the aminoalkyl side chain attached to the isourea moiety. Persicamidines A–E showed potent activity against hCoV‐229E and SARS‐CoV‐2 viruses in the nanomolar range together with very good selectivity indices, making persicamidines promising as starting points for drug development.