Properties and immunochemical reactivities of native and modified human-serum albumin.

Abstract

A series of chemically modified derivatives of human‐serum albumin has been produced in soluble monomeric form by modification of lysine, tryptophan, tyrosine, histidine, and acidic amino‐acid residues. Optical rotatory dispersion studies suggest that human‐serum albumin has a secondary structure which is resistant to many chemical side‐chain modifications. Sephadex‐gel‐filtration data and analytical ultracentrifugations indicate that the tertiary structure of human‐serum albumin is less resistant to chemical modification than the secondary structure. The combined data suggest that the secondary and tertiary structures to some extent are mutually independent. Lysine residues are found to be of major importance in the maintenance of the native tertiary structure.Chemically modified derivatives of human serum albumin are found to have decreased abilities to combine with the corresponding rabbit antibodies by a modified Farr technique. By immunoelectrophoresis and immunodiffusion a 96% acetylation was required to destroy complete immunogenic determinants. Lysine residues were found to be of major importance to the immunochemical reactivity of human‐serum albumin, while tryptophan, acidic amino acids and tyrosine residues play a minor role. Histidine residues seem to be unimportant to the immunochemical reactivity,Comparisons between immunochemical reactivities and structural parameters of native and modified albumins showed in particular a distinct relationship between the immunochemical reactivities and the Stokes‐radius values as determined by Sephadex‐gel filtration.