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Functionalisation of vitamin B12 derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria


Brenig, Christopher; Mestizo, Paula Daniela; Zelder, Felix (2022). Functionalisation of vitamin B12 derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria. RSC Advances, 12(44):28553-28559.

Abstract

This study describes the syntheses of four singly- and two doubly-modified vitamin B12 derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Coβ-phenyl-cobalamin-c,8-lactam and a 10-bromo-Coβ-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 B12 antagonists (10 nM) inhibit fully B12-dependent (0.1 nM) growth of L. delbrueckii. In contrast to potent 10-bromo-Coβ-phenylcobalamin, single modified 10-bromo-Coβ-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.

Abstract

This study describes the syntheses of four singly- and two doubly-modified vitamin B12 derivatives for generating antimetabolites of Lactobacillus delbrueckii (L. delbrueckii). The two most potent antagonists, a Coβ-phenyl-cobalamin-c,8-lactam and a 10-bromo-Coβ-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 B12 antagonists (10 nM) inhibit fully B12-dependent (0.1 nM) growth of L. delbrueckii. In contrast to potent 10-bromo-Coβ-phenylcobalamin, single modified 10-bromo-Coβ-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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > General Chemistry
Physical Sciences > General Chemical Engineering
Uncontrolled Keywords:General Chemical Engineering, General Chemistry
Language:English
Date:1 January 2022
Deposited On:17 Feb 2023 14:00
Last Modified:28 Jun 2024 01:42
Publisher:Royal Society of Chemistry
ISSN:2046-2069
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/d2ra05748d
PubMed ID:36320527
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)