Pseudo-complementary peptide nucleic acid (pcPNA) is a DNA analog in which modified DNA bases 2,6-diaminopurine (D) and 2-thiouracil (U_s) 'decorate' a poly[N-(2-aminoethyl)glycine] backbone, together with guanine (G) and cytosine (C). One of the most significant characteristics of pcPNA is its ability to effect double-duplex invasion of predetermined DNA sites inducing various changes in the biological and the physicochemical properties of the DNA. This protocol describes solid-phase synthesis of pcPNA. The monomers for G and C are commercially available, but the monomers for D and U_s need to be synthesized (or can be ordered to custom synthesis companies). Otherwise, the procedure is the same as that employed for Boc-strategy synthesis of conventional PNA. This protocol, if the synthesis of D and U_s monomers is not factored in, takes approximately 7 d to complete.