A5045181762- Helicobacter pylori-related gastroenterology studies
- Metalloenzymes and iron-sulfur proteins
- Biochemical and Molecular Research
- RNA modifications and cancer
- Inflammasome and immune disorders
- Epigenetics and DNA Methylation
- Metal complexes synthesis and properties
- Metal-Catalyzed Oxygenation Mechanisms
- Galectins and Cancer Biology
- Neuroendocrine Tumor Research Advances
- Gastroesophageal reflux and treatments
- Enzyme Structure and Function
- Cancer-related gene regulation
- Folate and B Vitamins Research
- Gastric Cancer Management and Outcomes
Albert Einstein College of Medicine
2019-2023
Aminofutalosine synthase (MqnE) catalyzes an important rearrangement reaction in menaquinone biosynthesis by the futalosine pathway. In this Letter, we report identification of previously unreported inhibitors MqnE using a mechanism-guided approach. The best inhibitor shows efficient inhibitory activity against H. pylori (IC50 = 1.8 ± 0.4 μM) and identifies as promising target for antibiotic development.
Antibiotic resistance continues to spread at an alarming rate, outpacing the introduction of new therapeutics and threatening globally undermine health care. There is a crucial need for strategies that selectively target specific pathogens while leaving majority microbiome untouched, thus averting debilitating sometimes fatal occurrences opportunistic infections. To address these challenges, we have adopted unique strategy focuses on oxygen-sensitive proteins, untapped set therapeutic...
A mouse model of human Familial Adenomatous Polyposis responds favorably to pharmacological inhibition 5'-methylthioadenosine phosphorylase (MTAP). Methylthio-DADMe-Immucillin-A (MTDIA) is an orally available, transition state analogue inhibitor MTAP. 5'-Methylthioadenosine (MTA), the substrate for MTAP, formed in polyamine synthesis and recycled by MTAP S-adenosyl-L-methionine (SAM) via salvage pathways. MTDIA treatment causes accumulation MTA, which inhibits growth head neck (FaDu) lung...
Helicobacter pylori is found in the gut lining of more than half world's population, causes gastric ulcers, and contributes to stomach cancers. Menaquinone synthesis H. relies on rare futalosine pathway, where 5′-methylthioadenosine nucleosidase (MTAN) proposed play an essential role. Transition state analogues MTAN, including BuT-DADMe-ImmA (BTDIA) MeT-DADMe-ImmA (MTDIA), exhibit bacteriostatic action against numerous diverse clinical isolates with minimum inhibitory concentrations (MIC's)...
Helicobacter pylori is a Gram-negative bacterium that responsible for gastric and duodenal ulcers. H. uses the unusual mqn pathway with aminofutalosine (AFL) as an intermediate menaquinone biosynthesis. Previous reports indicate hydrolysis of AFL by 5′-methylthioadenosine nucleosidase (HpMTAN) direct path producing downstream metabolites in pathway. However, genomic analysis indicates jhp0252 candidate encoding deaminase (AFLDA), activity deaminating aminofutolasine. The product, futalosine,...
Humans with Familial Adenomatous Polyposis (FAP) have increased risk of colon cancer. Mice the APCMin/+ mutation provide an animal model FAP. Interruption epigenetic control by preventing salvage S-adenosylmethionine from 5′-methylthioadenosine (MTA) was tested as a potential FAP therapy. 5′-Methylthioadenosine phosphorylase (MTAP) catalyzes phosphorolysis MTA to adenine and methylthioribose-1-phosphate for methionine recycling. The effect MTDIA, transition state analogue MTAP, oral agent in...