Publications by authors named "Lajos Z Szabo"
Article Synopsis
- Opioids, particularly those targeting the mu opioid receptor (MOR), are effective for severe pain but have serious side effects that limit their use.
- Researchers developed cyclic glycopeptide endomorphin (glycoEM) analogs that provided pain relief similar to morphine while reducing side effects, including lower abuse potential.
- In studies with male and female mice, two glycoEM analogs exhibited higher potency and longer-lasting pain relief at much lower doses than morphine, suggesting potential for future clinical applications.
Article Synopsis
- *While peptides often have better safety profiles, they face challenges with pharmacokinetics (PK), limiting their use in medicine.
- *Strategies like glycosylation, combined with other modifications, have been developed to enhance OT's effectiveness, selectivity, and stability in research models.
Article Synopsis
- Opioids are commonly used to treat both acute and chronic pain, but they come with serious side effects like constipation, dependence, respiratory issues, and overdose risks, contributing to the opioid crisis.
- There is a pressing need for non-addictive pain relief options, and oxytocin has emerged as a potential alternative for both pain management and prevention of opioid use disorder.
- New oxytocin analogues, created by altering its chemical structure for better stability and brain penetration, have demonstrated strong effectiveness in pain relief in mice, indicating promising clinical applications for future research.
The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize.
View Article and Find Full Text PDFIn 2014, almost 16 million tons of surfactants were used globally for cleaning and industrial applications. As a result, massive quantities disperse into environmental compartments every day. There is great market interest in developing highly biodegradable, less-toxic, and renewable alternatives to currently used petroleum-based surfactants.
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- - A new method has been developed to create pure β-S-glycopyranosides, a type of carbohydrate compound, using peracetate donors in the presence of InBr3 and chloroform.
- - The process involves deacylating the intermediates under specific conditions known as Zemplén conditions.
- - The study tested five different monosaccharides and disaccharides as donors and five types of thiols as acceptors, providing extensive data on the characteristics of the resulting compounds via techniques like NMR and mass spectrometry.
Hypoxia is a hallmark of solid tumors, is associated with local invasion, metastatic spread, resistance to chemo- and radiotherapy, and is an independent, negative prognostic factor for a diverse range of malignant neoplasms. The cellular response to hypoxia is primarily mediated by a family of transcription factors, among which hypoxia-inducible factor 1 (HIF1) plays a major role. Under normoxia, the oxygen-sensitive α subunit of HIF1 is rapidly and constitutively degraded but is stabilized and accumulates under hypoxia.
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- A new method for making Fmoc-serine and Fmoc-threonine glycosides is introduced to help with O-linked glycopeptide synthesis.
- Lewis acids are used to promote glycoside formation but can also cause unwanted reactions in the products.
- Using 'minimally competent' Lewis acids like InBr(3) effectively activates the reaction while reducing the unwanted side products from the sugar peracetates.
Article Synopsis
- Researchers designed small molecule inhibitors to target hypoxia-induced gene expression, with the potential for new tools in molecular biology and therapeutics.
- The study focuses on a specific antagonist, ETP 3, which disrupts the interaction between HIF-1α's transactivation domain and the p300/CBP coactivator.
- Results showed that ETP 3 effectively downregulated hypoxia-inducible gene expression in cultured cells in a dose-dependent manner.
Article Synopsis
- The study focuses on creating and analyzing a new class of compounds called xylylene-linked bis(1,4-piperazine-2,5-diones) to expand the chemical framework of existing piperazine-2,5-diones.
- The synthesis involved an efficient method resulting in unique solid-state structures, particularly noting how different side chain substitutions affect the molecular shapes.
- Findings show that certain intermolecular interactions create "C"-shaped monomers, while lack of these interactions leads to "S"-shaped conformations, highlighting the balance between attractive and repulsive forces in determining molecular structures.
Selective blockade of hypoxia-inducible gene expression by designed small molecules would prove valuable in suppressing tumor angiogenesis, metastasis and altered energy metabolism. We report the design, synthesis, and biological evaluation of a dimeric epidithiodiketopiperazine (ETP) small molecule transcriptional antagonist targeting the interaction of the p300/CBP coactivator with the transcription factor HIF-1alpha. Our results indicate that disrupting this interaction results in rapid downregulation of hypoxia-inducible genes critical for cancer progression.
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- Psorospermin, an antileukemic xanthone, is being developed to target DNA through topoisomerase II and alkylation for cancer treatment.
- Researchers synthesized new ring-constrained versions of psorospermin, using molecular modeling to evaluate their effectiveness in DNA interaction.
- Among the synthesized compounds, chlorohydrin 7 and epoxide 6 demonstrated higher cytotoxicity against human tumor cells compared to the natural product isohydroxypsorofebrin, with chlorohydrin retaining key alkylation properties despite its structural rigidity.