Tailored Pyridoxal Probes Unravel Novel Cofactor-Dependent Targets and Antibiotic Hits in Critical Bacterial Pathogens was written by Pfanzelt, Martin;Maher, Thomas E.;Absmeier, Ramona M.;Schwarz, Markus;Sieber, Stephan A.. And the article was included in Angewandte Chemie, International Edition in 2022.Electric Literature of C8H10NO6P The following contents are mentioned in the article:
Unprecedented bacterial targets are urgently needed to overcome the resistance crisis. Herein we systematically mine pyridoxal phosphate-dependent enzymes (PLP-DEs) in bacteria to focus on a target class which is involved in crucial metabolic processes. For this, we tailored eight pyridoxal (PL) probes bearing modifications at various positions. Overall, the probes exceeded the performance of a previous generation and provided a detailed map of PLP-DEs in clin. relevant pathogens including challenging Gram-neg. strains. Putative PLP-DEs with unknown function were exemplarily characterized via in-depth enzymic assays. Finally, we screened a panel of PLP binders for antibiotic activity and unravelled the targets of hit mols. Here, an uncharacterized enzyme, essential for bacterial growth, was assigned as PLP-dependent cysteine desulfurase and confirmed to be inhibited by the marketed drug phenelzine. Our approach provides a basis for deciphering novel PLP-DEs as essential antibiotic targets along with corresponding ways to decipher small mol. inhibitors. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Electric Literature of C8H10NO6P).
(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the 蟺-bonding aromatic system using its unhybridized p orbital. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the 蟽 bonds. Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Electric Literature of C8H10NO6P