Cobalamins and Mimics

Reactions with cobalamins and their mimics : mechanisms, synthetic applications and relevance to human health

---

Cobalamins and Mimics is founded on highly sucessful previous and on-going European contracts, including the TMR B₁₂ network and Cost Action D21/0008. The present network builds on this expertise, while extending the family of researchers.

The principal overall objectives are:

Specific objectives concern: New Mutases Involving the Adenosyl Radical as Initiator. The primary objective is to discover coenzyme B₁₂-dependent and independent analogues of reactions of the type catalysed by B₁₂-dependent mutases by searching a wide range of organisms from animals to bacteria. The secondary objective is to establish mechanisms of new B₁₂-dependent and ‘B₁₂-like’ processes.

The ultimate objective is to characterise the intermediates in the catalytic pathway and to define with atomic precision the mechanism of the molecular rearrangement.

Enzymatic Reactions Involving Cob(I)alamin or an Analogue.

The primary objective is to elucidate mechanisms of methyl transferases, dehalogenases and related enzymes. The secondary objective is to determine the nature of the intermediates in these reactions.

Enzymatic Reactions that Proceed via ‘B₁₂-like’ Mechanisms.

The primary objective is to define the complete reaction pathways for coenzyme B₁₂-independent 2- and 4-hydroxyacid dehydratases. The secondary objective is to develop the conversion of hydroxyacid substrate into product alpha-beta-unsaturated acid as a clean industrial scale process.

Model Systems.

The objective is to replicate all of the main features of the enzymatic reactions described above in carefully designed model systems.

B₁₂ in Toxicology.

The primary objective is to develop cob(I)alamin and its mimics as supernucleophilic reagents for the sensitive detection of toxins in environmental and biological samples, including foods. The secondary objective is to apply cob(I)alamin for the measurement of DNA damage by such toxins or their metabolites. The third objective is to test whether cob(I)alamin acts as an in vivo scavenger of electrophiles.

Partner web-sites:

Newcastle
Graz
Innsbruck
Jena
Karlsruhe
Maccelsfield
Marburg
Stockholm

Associates web-sites:
Antwerp
Bangor
Budapest
Surrey
Ulm
Vienna