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Functionalisation of vitamin B(12) derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria

This study describes the syntheses of four singly- and two doubly-modified vitamin B(12) derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Co(β)-phenyl-cobalamin-c,8-lactam and a 10-bromo-Co(β)-phenylcobalamin combine a c-lac...

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Detalles Bibliográficos
Autores principales: Brenig, Christopher, Mestizo, Paula Daniela, Zelder, Felix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9541496/
https://www.ncbi.nlm.nih.gov/pubmed/36320527
http://dx.doi.org/10.1039/d2ra05748d
Descripción
Sumario:This study describes the syntheses of four singly- and two doubly-modified vitamin B(12) derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Co(β)-phenyl-cobalamin-c,8-lactam and a 10-bromo-Co(β)-phenylcobalamin combine a c-lactam or 10-bromo modification at the “eastern” site of the corrin ring with an artificial organometallic phenyl group instead of a cyano ligand at the β-site of the cobalt center. These two doubly-modified B(12) antagonists (10 nM) inhibit fully B(12)-dependent (0.1 nM) growth of L. delbrueckii. In contrast to potent 10-bromo-Co(β)-phenylcobalamin, single modified 10-bromo-Co(β)-cyanocobalamin lacking the artificial organometallic phenyl ligand does not show any inhibitory effect. These results suggest, that the organometallic β-phenyl ligand at the Co center ultimately steers the metabolic effect of the 10-bromo-analogue.