Macrocyclic tetrapeptide complex

DR. RALPH WILKINS (New Mexico State University) What is the rate of the reaction of trien with your copper macrocyclic tetrapeptide complex Based on your mechanism it should be... 

To achieve selectivity in a classical metal-binding HDAC inhibitor, the cap needs to contain functionality for additional interactions with the rim . Of the inhibitors described above, the cyclic tetrapeptides have this potential due to their large macrocyclic scaffold, but have yet to result in clinical candidates. Structurally, the most complex HDAC inhibitors are the depsipeptide natural products exemplified by FK228. These compounds, which are treated separately in the next section, have even more elaborate caps , and are the best-documented example of selective HDAC inhibitors. 

The first approach in the synthesis of a bifunctional DOTA-derivative is to start with a tetrapeptide. This precursor may be obtained by a peptide route. The treatment with borane to convert the peptide to a linear polyamino alcohol, followed by tosylation and cyclization leads to the macrocycle (O Fig. 45.9). The modification for the coupling of the final BFC to a biomolecule is introduced already at the begiiming with the choice of the first amino acid. The final alkylation of the amines of the macrocycle leads to a BFC with four acetic acid groups for the complexation of the radiometal (Moi and Meares 1988). 

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