A Study of Cross-Linkage of Formaldehyde with Human Serum Albumin

It's well known that irreversible cross-linked complexes between proteins, produced by formaldehyde interacting with free amino or amide groups to form Schiff s base, are formed in diabetes and aging patients. To identify such specific modified peptides as biomarkers for clinical diagnose of diabetes and AD, cross-linkage of formaldehyde with human serum albumin (HSA) was analyzed by LC/ESI/MS in this study. Eighteen peptides as important biomarkers were identified and the corresponding possible structures of their cross-linkages were also analyzed. Five of those peptides were modified by the reaction of one molecular proportion of formaldehyde with one molecular proportion of amino group. Reaction of one molecular proportion of formaldehyde with two molecular proportions of amino groups were found in 4 of the 18 peptides. In the rest 9 peptides, the structures of the cross-linkages of formaldehyde with amino groups was more complex. Furthermore, several lysine and arginine residues of those peptides were proved as modification sites in HSA cross-linked with formaldehyde.