Examining Mn-Peptide Complexes Applied to the Preparation of Irradiated Vaccines

Antioxidant Mn-peptide complexes accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans have a remarkable ability - they protect the structure and functions of proteins exposed to massive doses of ionizing radiation, but they do not significantly protect nucleic acids. We designed a decapeptide DEHGTAVMLK (DP1) whose amino acid composition was selected to include most of the prevalent amino acids in the protective fraction of D. radiodurans cell extracts. DP1 spontaneously forms antioxidant complexes with Mn2+ and orthophosphate (MDP) which uncouple protein damage from DNA/RNA damage during supralethal exposures to gamma-radiation. This approach has been applied to the preparation of irradiated vaccines. An ideal whole-organism vaccine lacks any infectivity, but retains all original epitopes needed to mount a protective immune response. Indeed, MDP preserves antigenic structures in aqueous preparations of lethally-irradiated viruses and bacteria. The structure/function relationships of DP1 were interrogated by LC/MS and HPLC. Upon exposure to gamma-rays, the radiation-dependent decay of DP1 correlates to the loss of protective ability of proteins. Interaction between DP1 and Mn was examined in aqueous solution by nuclear magnetic resonance and electron nuclear double resonance spectroscopy. Several amino acids in DP1 are more important for MDP complex formation than others.