In 2018,Biochemistry included an article by Hinchliffe, Philip; Tanner, Carol A.; Krismanich, Anthony P.; Labbe, Genevieve; Goodfellow, Valerie J.; Marrone, Laura; Desoky, Ahmed Y.; Calvopina, Karina; Whittle, Emily E.; Zeng, Fanxing; Avison, Matthew B.; Bols, Niels C.; Siemann, Stefan; Spencer, James; Dmitrienko, Gary I.. Application In Synthesis of 2-(Bromomethyl)pyridine hydrobromide. The article was titled 《Structural and Kinetic Studies of the Potent Inhibition of Metallo-β-lactamases by 6-Phosphonomethylpyridine-2-carboxylates》. The information in the text is summarized as follows:
There are currently no clin. available inhibitors of metallo-β-lactamases (MBLs), enzymes which hydrolyze β-lactam antibiotics and confer resistance on Gram-neg. bacteria. Here we present 6-phosphonomethylpyridine-2-carboxylates (PMPCs) as potent inhibitors of subclass B1 (IMP-1, VIM-2, NDM-1) and B3 (L1) MBLs. Inhibition followed a competitive, slow-binding model without an isomerization step (IC50 values 0.3 – 7.2 μM; Ki 0.03 – 1.5 μM). Min. inhibitory concentration assays demonstrated potentiation of β-lactam (meropenem) activity against MBL-producing bacteria, including clin. isolates, at concentrations where eukaryotic cells remain viable. Crystal structures revealed unprecedented modes of inhibitor binding to B1 (IMP-1) and B3 (L1) MBLs. In IMP-1, binding does not replace the nucleophilic hydroxide and the PMPC carboxylate and pyridine nitrogen interact closely (2.3 and 2.7 Å, resp.) with the Zn2 ion of the binuclear metal site. The phosphonate group makes limited interactions, but is 2.6 Å from the nucleophilic hydroxide. Furthermore, the presence of a water mol. interacting with the PMPC phosphonate and pyridine N-C2 π-bond, as well as the nucleophilic hydroxide, suggests that the PMPC binds to the MBL active site as its hydrate. Binding is markedly different in L1, with the phosphonate displacing both Zn2, forming a monozinc enzyme, and the nucleophilic hydroxide, while also making multiple interactions with the protein main chain and Zn1. The carboxylate and pyridine nitrogen interact with Ser221/223, resp. (3 Å distance). The potency, low toxicity, cellular activity and amenability to further modification of PMPCs indicate these and similar phosphonate compounds can be further considered for future MBL inhibitor development. The experimental process involved the reaction of 2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8Application In Synthesis of 2-(Bromomethyl)pyridine hydrobromide)
2-(Bromomethyl)pyridine hydrobromide(cas: 31106-82-8) belongs to pyridine. Pyridine derivatives lend themselves to many roles in the spirited field of supramolecular chemistry – whether as the ligand backbone of metal-organic polymers or presiding over the key electronic stations of nanodevices. In biochemistry, pyridine-containing cofactors are necessary nutrients on which our lives depend. Application In Synthesis of 2-(Bromomethyl)pyridine hydrobromide