A 12-Porphyrin System: Syntheses of Peptide Porphyrins with Multiple Histidines and the Aggregation Behavior in the Presence of Hemin.

We succeeded in combining multiple-histidine peptides with porphyrins; that is to say, we synthesized three peptide porphyrins consisting of α4-meso-tetrakis(o-aminophenyl)porphyrin, α4-H2TAPP, and amphiphilic peptide, α4-(PepA18)n(AG)4−n-H2TAPP (n = 1, 3, and 4; PepA18 = EEALEKHEKALEKHEKAG), in the liquid phase. These compounds were designed to construct multiple porphyrin systems; in other words, each peptide attached on the H2TAPP was designed to contain two histidines. The stability of the porphyrins, (AG)4-H2TAPP and (AG)1(Boc-AG)3-H2TAPP, as well as the coupling conditions between the porphyrin fragments and the 16-residue peptide, EEALEKHEKALEKHEK, to give α4-(PepA18)n(AG)4−n-H2TAPP (n = 1, 3, and 4) were studied in detail with respect to the temperature, solvents, coupling reagents, additives, and amines. This search revealed that the combination of DMF/benzotriazol-1-yl-oxy-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP)/N,N-diisopropylethylamine is suitable for the purpose. The search a...