Abstract
Background:
Ionizing radiation causes the generation of damaging reactive oxygen species that lead to cellular damage and death. Organisms such as Deinococcus radiodurans have evolved mechanisms for extreme resistance to ionizing radiation, and resistance has been shown to be a consequence of protection of critical proteins from oxidative inactivation.
Objectives:
D. radiodurans accumulates high levels of manganese and of small peptides that together are protective. Our aim was to rationally design antioxidant peptides.
Methods:
Amino acid analysis was utilized to determine the rates of loss of the 20 amino acids exposed to varying doses of irradiation. The activity of glutamine synthetase and methionine sulfoxide reductase was assayed to follow their inactivation by irradiation.
Results:
The ability of an amino acid to protect enzymes from inactivation by ionizing radiation paralleled its sensitivity to ionizing radiation. Based on this observation and the ability of histidine to confer water solubility, we synthesized the hexapeptide His-Met-His-Met-His-Met and found that it provided markedly increased protection against irradiation.
Discussion:
Small peptides containing histidine and methionine were readily soluble and provided enzymes with remarkable protection from inactivation by ionizing radiation.
Keywords:
Amino acid oxidation; Histidine; Ionizing radiation; Methionine; Radioprotection.