Aromatic Side Chain−Porphyrin Interactions in Designed Hemoproteins

Abstract

Aromatic amino acid side chains are commonly observed to interact with the heme cofactors of natural hemoproteins. These interactions are of the types previously identified for pairs or groups of aromatic amino acid side chains in proteins: offset π-stacking and T-stacking (an edge-to-face arrangement). To evaluate how such interactions may influence structural stability of hemoproteins, we synthesized peptide-sandwiched mesohemes (PSMs) 2 and 3 in which the alanine-4 (Ala-4) residues in 1 have been replaced by phenylalanine (Phe) and tryptophan (Trp), respectively. The Co(III) analogues of 1, 2, and 3 (1-Co, 2-Co, and 3-Co, respectively) were also prepared. Histidine (His)-to-iron coordination in 1 had previously been shown to induce helical conformations in the peptides (helix content ∼50% at 8 °C). Molecular modeling studies suggested that Trp, but not Phe, could engage in edge-to-face interactions with the porphyrin if the peptides are fully helical. Replacing Ala-4 with Trp, but not with Phe, was th...