Warheads tetrapeptides

The initial compounds, both from natural sources and synthesis were relatively simple structures consisting of a zinc-binding warhead (a hydroxamate or epoxide), a 4-carbon linker (mimicking the e-amino side chain of lysine) and an aromatic end . However, within the original natural product structures was a tetrapeptide known as trapoxin A (Figure 1.8, 66), first reported by Itazaki et al. in 1990, with recognition of the mechanism of action, irreversible inhibition of deacetylation of acelylated histone molecules, being published by Kijima et al. three years later. ... 

The Cyclic Tetrapeptide Natural Products with a Ketone Warhead... 

Figure 4.7 Structures of cyclic tetrapeptide HDAC inhibitors with a common epoxyketone zinc binding warhead.

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