Hydroxyethylation of amino acids in plasma albumin with ethylene oxide

The reaction of ethylene oxide with amino acids in bovine plasma albumin was studied under various conditions of pH and time. Ethylene oxide reacted with arginyl, cystyl, histidyl, lysyl, methionyl and tyrosyl residues in albumin. The maximal reaction of arginyl, histidyl, lysyl and tyrosyl residues occurred at pH values equal to or greater than the pK of the respective reacting groups.

The reaction of ethylene oxide with the above amino acid residues resulted in the formation of 21 new peaks detected by chromatograpic analysis of the amino acids. The amino acids from which most of these products originated were detected by labeling the albumin biosynthetically with individual radioactive amino acids before hydroxyethylation. The major product of hydroxyethylation of lysine was apparently Nϵ[tris(2-hydroxyethyl)]lysine, since it corresponded to the Nϵ[tris(2-hydroxyethyl)]-lysine, prepared by direct synthesis, with respect to mobility in several chromatographic systems.

The accessibility of some lysyl and methionyl residues in albumin to ethylene oxide may be dependent upon a partial change in the tertiary structure of albumin, resulting from the reaction of cystyl residues in albumin with ethylene oxide.