Discovery of 5α-pregnan-2β,3α-diol-20-one as a neuroHIV Protective Agent

Presenter: Md Imdadul Khanhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1009/thumbnail.jp

Development of L-γ-Methyleneglutamine-based compounds for cancer

Presenter: Md. Imdadul H. Khanhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1014/thumbnail.jp

PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution

Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly of DNA-binding transcription factors (TF), leading to recruitment of co-activators such as CBP/p300 to modify the local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator recruitment relationships remain unmapped. Here, studying the oncogenic fusion TF PAX3-FOXO1 (P3F) from alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in the activation domain (AD) of P3F is important for a small alpha helical coil that recruits CBP/p300 to chromatin. P3F driven transcription requires both this single cysteine and CBP/p300. Mutants of the cysteine reduce aRMS cell proliferation and induce cellular differentiation. Furthermore, we discover a profound dependence on CBP/p300 for clustering of Pol2 loops that connect P3F to its target genes. In the absence of CBP/p300, Pol2 long range enhancer loops collapse, Pol2 accumulates in CpG islands and fails to exit the gene body. These results reveal a potential novel axis for therapeutic interference with P3F in aRMS and clarify the molecular relationship of P3F and CBP/p300 in sustaining active Pol2 clusters essential for oncogenic transcription

Synthesis of 3,4,5-Trisubstituted Isoxazoles in Water via a [3+2]-Cycloaddition of Nitrile Oxides and 1,3-Diketones, β-Ketoesters, or β-Ketoamides: Base-mediated and Keto-enol-controlled Mechanism

A selective [3+2]-cycloaddition reaction of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides in water without the need of a metal catalyst is described. The selectivity of the reaction can be controlled by the polarity of solvents in the presence of an appropriate base. The optimized reaction condition circumvents other reactions, such as O-imidoylation or hetero [3+2]-cycloaddition. The reaction happens fast in water to provide an environment friendly access to 3,4,5-trisubstituted isoxazoles, specifically acyl-substituted, ester-substituted, or amide-substituted isoxazoles, which are important structures found in numerous bioactive natural products and pharmaceuticals

New Hydroxy-1,4-naphthoquinone and Phenoxy-phenyl-naphthoquinone Compounds as Drug-resistant Antimalarials

Presenter: Benjamin Sawyerhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1010/thumbnail.jp