Cyclic and hairpin peptide complexes of heme

J Am Chem Soc. 2002 Oct 23;124(42):12394-5. doi: 10.1021/ja020912w.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Disulfides / chemistry
  • Heme / chemistry*
  • Kinetics
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemistry*
  • Protein Conformation

Substances

  • Disulfides
  • Peptides, Cyclic
  • Heme