title: Cyclic and hairpin peptide complexes of heme.
abstract: We have synthesized and characterized a new class of heme-peptide complexes using disulfide-linked hairpin-turn and cyclic peptides and compared these to their linear analogues. The binding affinities, helicities, and mechanism of binding of linear, hairpin, and cyclic peptides to [FeIII(coproporphyrin-I)]+ have been determined. In a minimalist approach, we utilize amphiphilic peptide sequences (15-mers), where a central histidine provides heme ligation, and the hydrophobic effect is used to optimize heme-peptide complex stability. We have incorporated disulfide bridges between amphiphilic peptides to make hairpin and even cyclic peptides that bind heme extremely well, roughly 5 x 106 times more strongly than histidine itself. CD studies show that the cyclic peptide heme complexes are completely alpha-helical. NMR spectra of paramagnetic complexes of the peptides show that the 15-mer peptides bind sequentially, with an observable monopeptide, high-spin intermediate. In contrast, the cyclic peptide complexes ligate both imidazoles cooperatively to the heme, producing only a low-spin complex. Electrochemical measurements of the E1/2 of the FeIII(coproporphyrin-I)+ complexes of these peptides are all at fairly low potentials, ranging from -215 to -252 mV versus NHE at pH 7.
authors.affiliation: School of Chemical Sciences, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Rosenblatt
authors.forename: David L
authors.initials: DL
authors.lastname: Huffman
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Wang
authors.forename: Henriette A
authors.initials: HA
authors.lastname: Remmer
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Suslick
mesh_terms: D004220:Disulfides / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D004220:Disulfides; D010456:Peptides, Cyclic; D006418:Heme