Publications by authors named "D T Keough"
Article Synopsis
- MYC is a critical driver of cancer that enhances gene expression and increases RNA production, contributing to tumor growth and survival.
- The study reveals that MYC triggers RNA degradation, leading to toxic byproducts that cause cancer cell death, indicating a new mechanism for targeting MYC-driven cancers.
- Therapeutic strategies that intensify the breakdown of RNA could serve as effective treatments for aggressive cancers like triple-negative breast cancer (TNBC) that rely on MYC.
Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by and , , , and . Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have values ranging from 3 nM to >10 μM, depending on the structure of the inhibitor and the biological origin of the enzyme.
View Article and Find Full Text PDFTwelve N2'-branched acyclic nucleoside phosphonates and bisphosphonates were synthesized as potential inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPRT), the key enzyme in the purine salvage pathway for production of purine nucleotides. The chemical structures were designed with the aim to study selectivity of the inhibitors for PfHGXPRT over human HGPRT. The newly prepared compounds contain 9-deazahypoxanthine connected to a phosphonate group via a five-atom-linker bearing a nitrogen atom (N2') as a branching point.
View Article and Find Full Text PDFArticle Synopsis
- Pathogens like certain spp. cannot produce purine nucleobases on their own and depend on host cells to acquire them for DNA/RNA synthesis, utilizing purine phosphoribosyltransferases (PRTs) as key enzymes in this process.
- Researchers synthesized 16 new acyclic nucleoside phosphonates, including several with unique chiral centers, to test their inhibitory effects on PRTs.
- The most effective inhibitor, bisphosphonate (,)-, demonstrated exceptional potency against both human and parasite 6-oxopurine PRTs, with a very low inhibition constant (2 nM), and its varying binding conformations explain its effectiveness and preference for targeting parasite enzymes over human ones (35-fold select
(Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA.
View Article and Find Full Text PDF