《Hit-to-lead optimization of a latency-associated nuclear antigen inhibitor against Kaposi’s sarcoma-associated herpesvirus infections》 was written by Kirsch, Philine; Stein, Saskia C.; Berwanger, Aylin; Rinkes, Julia; Jakob, Valentin; Schulz, Thomas F.; Empting, Martin. Recommanded Product: 2-Hydroxyphenylboronic acid And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:
The Latency-associated nuclear antigen (LANA) plays a central role for the latent persistence of the Kaposi’s Sarcoma Herpesvirus (KSHV) in the human host and helps to establish lifelong infections. Herein, we report our efforts towards hit-to-lead generation starting from a previously discovered LANA-DNA inhibitor. By tethering the viral genome to the host nucleosomes, LANA ensures the segregation and persistence of the viral DNA during mitosis. LANA is also required for the replication of the latent viral episome during the S phase of the cell cycle. We aim to inhibit the interaction between LANA and the viral genome to prevent the latent persistence of KSHV in the host organism. Medicinal chem.-driven optimization studies and structure-activity-relationship investigation led to the discovery of an improved LANA inhibitor. The functional activity of our compounds was evaluated using a fluorescence polarization (FP)-based interaction inhibition assay and electrophoretic mobility shift assay (EMSA). Even though a crystal structure of the ligand protein complex was not available, we successfully conducted hit optimization toward a low micromolar protein-nucleic acid-interaction inhibitor. Addnl., we applied STD-NMR studies to corroborate target binding and to gain insights into the binding orientation of our most potent inhibitor, providing opportunities for further rational design of more efficient LANA-targeting anti KSHV agents in future studies. After reading the article, we found that the author used 2-Hydroxyphenylboronic acid(cas: 89466-08-0Recommanded Product: 2-Hydroxyphenylboronic acid)
2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. Recommanded Product: 2-Hydroxyphenylboronic acid
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