Artificial Transaminases Linking Pyridoxamine to Binding Cavities: Controlling the Geometry

A transaminase mimic joining a pyridoxamine unit to a cyclodextrin by a single linkage is quite selective for the conversion of phenylpyruvic acid to phenylalanine, compared with its reactivity toward nonbinding ketoacids. The selectivity is even greater with 4-tert-butylphenylpyruvic acid but is essentially erased with a phenylpyruvic acid carrying a tert-butyl group in the meta position. This strong geometric preference can be modified with transaminase mimics in which the pyridoxamine is joined to cyclodextrin by two links, greatly restricting the freedom of the system. A transaminase has also been prepared with the pyridoxamine unit doubly linked to a synthetic macrocyclic hydrophobic cavity, which has yet other geometric preferences. The doubly linked pyridoxamine units were prepared by use of a novel synthetic procedure for the conversion of olefins to vic-dithiols. An improved procedure for the preparation of β-cyclodextrin 6A,6B diiodide is also described.