Chemical modifications of the protein of carcinoembryonic antigen: associated changes in immunological activity and conformation

Abstract

Chemical substitution of the exposed residues of tryptophan, tyrosine, histidine and arginine in carcinoembryonic antigen (CEA), using appropriately selective reagents, caused no significant change in the capacity of the antigen to bind to anti-CEA serum. However, treatments of CEA with 2-hydroxy-5-nitrobenzyl bromide and tetranitromethane, both in the presence of guanidine HCl, caused a large reduction in binding capacity. Measurement of the circular dichroism spectra of all of the products showed that retention of conformation of the molecular correlated well with retained antigenic activity, whereas the large losses in capacity to bind to anti-CEA sera were accompanied by a probably the result of gross conformational changes. The tyrosine residues of CEA may be classified into three categories: (i) 3 freely reacting residues, (ii) 7 or 8 moderately buried residues and (iii) 15 unreactive residues.

Carcinoembryonic antigen: Function in metastasis by human colorectal carcinoma

“…[2,3,4].) Circular dichroism studies of CEA showed that 80% of the molecule is made up of 13 structure and [5 turn, with the other 20% in random coil conformation [20]. Two of them, TM2 and TM4, are similar to NCA, while TM1 and TM3 contain the first disulphide bridge domain plus part of the second from CEA.…”

Ability of CEA blood levels to reflect tumour burden: a study in a human xenograft model

“…The CEA used was isolated from hepatic metastases of a human colonic carcinoma and purified to satisfy criteria described by Westwood & Thomas (1975) and Westwood et al (1978). Anti-CEA sera were raised in a rabbit by the method described by .…”

Carcinoembryonic Antigen, Its Spatial Structure and Localization of Antigenic Determinants

“…Earlier [21], the antigenic activity was found to be unchanged following modifica tion of histidine residues accompanied by some alterations of the conformation of anti gen [22], This discrepancy appeared to be connected with the application earlier [21,22] of the antiserum obtained against the protein portion of CEA. This version ap peared likely to be due to the fact that the previous investigations [21,22] were carried out using CEA isolated by extraction with perchloric acid.…”

“…This version ap peared likely to be due to the fact that the previous investigations [21,22] were carried out using CEA isolated by extraction with perchloric acid. As was mentioned above, this extraction is accompanied by an altera tion of the conformation of the molecule.…”