SITE-SPECIFIC N-TERMINAL AUTO-DEGRADATION OF HUMAN SERUM-ALBUMIN

Human serum albumin prepared by blood fractionation for clinical purpo ses was found to degrade when stored at or above 30 degrees C. Mass sp ectrometry and N-terminal sequencing of the protein identified degrada tion corresponding to the loss of the first two residues, aspartic aci d and alanine. The reaction was shown to be dependent upon temperature and the N-terminal alpha-amino group. In addition, comparison with se rum albumins derived from other species showed that the instability of the N-terminus was specific to the human albumin sequence. An intact aspartyl-alanyl dipeptide, purified from degraded albumin solutions, d iffered substantially from a synthetic dipeptide on amino acid analysi s, N-terminal sequencing and NMR. It is suggested that the released di peptide may be cyclic, implying a novel cleavage mechanism.