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.Application In Synthesis of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate 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: 54-47-7Application In Synthesis of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate).
(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C鈥揌 in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Application In Synthesis of (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate