Scheme 1.

Synthesis of PNA 1 (left) and histone peptide 2 (right), followed by the ligation to create PNA-peptide chimera 3. Reaction conditions: (a). 20 mM NaNO₂, 6 M GnHCl, 0.2 M phosphate buffer pH = 3, 0° C, 20 min. (b). 50 mM MESNa, 100 mM thiophenol, 6 M GnHCl, 0.2 M phosphate buffer pH = 7.5. Below is the structure of the full construct 3, and the mass spectrum of the purified product. Note that histone peptide 2 has the tripeptide GYK appended to it; see Supporting Information for synthetic details and compound characterization.