The Exchange Stability of Cobalt in Vitamin B<sub>12</sub>

Boos, R. N.; Rosenblum, Charles; Woodbury, David T.

doi:10.1021/ja01155a509

Cited by 17 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the affinity of Co III and Co II for porphyrins and, even more, for corrins is very high [12] (demetalated only in H 2 SO 4 100 %, 2 h, 25°C [11] ). So, this enzyme cofactor is not expected to be demetalated under physiological conditions, even in the presence of chelators such as TDMQ20 or TDMQ22.…”

Section: Tdmq20 or Tdmq22 + Vitamin B12mentioning

confidence: 99%

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12

et al. 2019

View full text Add to dashboard Cite

Copper chelators based on a tetradentate monoquinoline (TDMQ) scaffold are currently developed as potential drugs against Alzheimer's disease. Since TDMQ chelators have a high affinity for CuII and are expected to regulate copper homeostasis in the brain, the question whether these chelators might be able to demetalate, and therefore inhibit, essential copper proteins is obviously important, and should be answered before clinical development could be considered. We therefore examined the possible interaction of these chelators with physiological copper proteins, and related metal biomolecules. Our present work evidenced that TDMQ chelators (up to millimolar concentrations) do not affect in vitro the catalytic activities of Cu,Zn‐superoxide dismutase and tyrosinase, two copper enzymes expressed in the brain and involved in the regulation of redox processes. In addition, TDMQ were found unable to demetalate vitamin B12, a CoIII cofactor essential for neurotransmitter synthesis and normal brain function. The validation of the compatibility between TDMQs and several physiological metal complexes is an important positive issue supporting the development of TDMQ chelators as drug‐candidates.

show abstract

Section: Tdmq20 or Tdmq22 + Vitamin B12mentioning

confidence: 99%

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12

et al. 2019

View full text Add to dashboard Cite

show abstract

“…An example for such species is the Co containing vitamin B 12 (Guillard and Cassie, 1963) which had been reported to be inert to metal-exchange (Boos et al, 1951). Various bacteria, including the cyanobacteria Synechococcus and C. watsonii are known to produce significant amounts of B 12 (Bertrand et al, 2011;Bonnet et al, 2010;Carlucci and Bowes, 1970) and recent metagenomic analysis has suggested that archaea may also be responsible for B 12 production in some ocean regions (Doxey et al, in press).…”

Section: Possible Source and Identity Of The Ligand-exchange Inert Comentioning

confidence: 99%

Dissolved cobalt speciation and reactivity in the eastern tropical North Atlantic

Baars

Croot

2015

Marine Chemistry

View full text Add to dashboard Cite

“…From this point of view, DPA and TDMQ20 exhibited similar behaviors. In fact, the affinity of Co III and Co II for porphyrins and, even more, for corrins is very high [ 33 ] (demetallated only in H 2 SO 4 100%, 2 h, 25 °C [ 34 ]). Therefore, this enzyme cofactor is not expected to be demetallated under physiological conditions, even in the presence of potent chelators.…”

Section: Resultsmentioning

confidence: 99%

The Specific Copper(II) Chelator TDMQ20 Is Efficient for the Treatment of Wilson’s Disease in Mice

Zhu,

Tang,

Huang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

(1) Background: In patients with Wilson’s disease, the deficiency of the copper carrier ATP7B causes the accumulation of copper in the liver, brain and various other organs. Lifelong treatment is therefore mandatory, using copper chelators to increase the excretion of copper and to avoid life-threatening damage. The clinically used reference drug, D-penicillamine, exhibit numerous adverse effects, especially a frequent severe and irreversible neurological worsening, mainly due to its lack of metal selectivity; (2) Methods: A new tetradentate ligand based on an 8-aminoquinoline entity, named TDMQ20, which is highly selective for copper compared with other metal ions, is evaluated in “toxic milk” TX mice as an oral treatment of this Wilson’s disease murine model; (3) Results: The concentration of copper in the liver of “toxic milk” TX mice decreased and the fecal excretion of copper increased upon oral treatment with TDMQ20. Both effects are dose-dependent, and more pronounced than those of D-penicillamine; (4) Conclusions: The TDMQ20 copper chelator is more efficient than the reference drug D-penicillamine for the treatment of a Wilson’s disease murine model. Pharmacological data obtained with TDMQ20 on the TX mouse model strongly support the selection of this ligand as a drug candidate for this genetic disease.

show abstract

The Exchange Stability of Cobalt in Vitamin B₁₂

Cited by 17 publications

References 2 publications

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12

Dissolved cobalt speciation and reactivity in the eastern tropical North Atlantic

The Specific Copper(II) Chelator TDMQ20 Is Efficient for the Treatment of Wilson’s Disease in Mice

Contact Info

Product

Resources

About

The Exchange Stability of Cobalt in Vitamin B12

Cited by 17 publications

References 2 publications

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the CoIII Cofactor Vitamin B12

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the CoIII Cofactor Vitamin B12

Dissolved cobalt speciation and reactivity in the eastern tropical North Atlantic

The Specific Copper(II) Chelator TDMQ20 Is Efficient for the Treatment of Wilson’s Disease in Mice

Contact Info

Product

Resources

About

The Exchange Stability of Cobalt in Vitamin B₁₂

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12

The TDMQ Regulators of Copper Homeostasis Do Not Disturb the Activities of Cu,Zn‐SOD, Tyrosinase, or the Co^III Cofactor Vitamin B12