Synthesis and Activity of Oxygen-Carrying Heme Peptides

Development of effective resuscitation agents for blood-loss replacement in trauma or surgery is extremely important. We synthesized 15 peptides (test peptides) that were designed on the basis that the heme group in myoglobin (Mb) and hemoglobin (Hb) is sandwiched between helices E and F. The abilities of the test peptides and 6 control peptides to form stable complexes with heme were investigated. None of the controls bound heme. However each of the test peptides was able to form 1:1 coordinate complexes with heme, which were stable to manipulation and behaved as a single molecular species. The reduced peptide-heme complexes bound oxygen and gave visible spectra that were typical of oxygenated heme-proteins The heme-peptides gave hyperbolic oxygen- saturation curves, but showed slightly different P5O values. They were administered into mice, either as emulsions in adjuvant or intravenously in PBS. Injection with adjuvant stimulated antipeptide antibody responses, which bound to the correlate protein (Mb or Hb). But the peptides were non-immunogenic when administered intravenously in PBS.