The extensive NMR investigations reveal the presence of E-isomers in the derivative of N′-benzylidenebenzohydrazide. The different conformer populations are controlled by the strength of intramolecular hydrogen bonds.

The ternary ion-pair complexation protocol for rapid testing of the enantiopurity and the assignment of absolute configurations of various acid and ester derivatives.

A series of N-benzoylanthranilamide derivatives have been synthesized with the substitution of competitive HB acceptors and investigated by NMR spectroscopy and single crystal XRD.

Prostate cancer (PCa) is characterized by the complexity of oncogenic signaling and heterogeneity of transcriptional landscapes. Adaptor protein ABI1 is a tumor suppressor in PCa, as evidenced by its loss or downregulation in high-grade and metastatic tumors. STAT3 activation is a hallmark of high-risk prostate tumors. ABI1 loss is associated with STAT3 activation leading to transcriptional reprogramming and epithelial-mesenchymal-transition (EMT) of prostate cancer cells (Nath, Li et al. Cell Commun Signal. 2019). EMT changes involve several homeobox transcription factors. The fact that ABI1 contains a homeobox homology region (HHR) suggests the possibility that it plays a role in EMT by directly regulating transcriptional activity by DNA binding. To examine this hypothesis, we set out to analyze ABI1-DNA binding. Structural NMR studies and in-vitro protein-DNA binding assays confirmed ABI1 binding to DNA regulated by alternative spliced ABI1 Exon 4 region located on the C-terminus of ABI1 HHR. RNA-sequencing data and PCa cell lines qPCR assays reveal the alternative ABI1 Exon 4 spliced-in is enriched in high Gleason-scored PCa samples. ABI1 and STAT3 co-regulate their nuclear vs. cytoplasm localization, and the subsequent functional studies using PCa lines expressing wild type or HHR Exon 4 deletion mutant of ABI1 demonstrated that HHR regulates the STAT3 DNA binding patterns, STAT3 mediated chromatin structure programming as well as its transcription activities. We propose that ABI1 is a critical regulator of STAT3 activity during prostate cancer progression. Citation Format: Xiang Li, Neeru Arya, Baylee A. Porter, Allysa P. Kemraj, Xuesen Dong, Dominique Frueh, Alaji Bah, Leszek Kotula. ABI1 regulates STAT3 transcription through a DNA binding activity. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3725.

No abstract