Structure and genetic engineering of antigens and antibodies: Applications in immunoassays

Abstract

Proteins play central roles in all life processes, catalyzing biochemical reactions with remarkable specificity and serving as key structural elements in all cells and tissues. Proteins are involved in every aspect of life: catalysis, structure, motion, recognition, regulation. We now know of many thousands of protein sequences. Recent advances in gene synthesis and genetic engineering have made it possible in principle to construct any desired amino acid sequence. Protein engineering can be used both to explore fundamental questions regarding protein folding, structure ,,,4 C..,,r:,, . . . &,. ,.I,,:, .._,.C., ___c_:_._ 4-_.--J:-,., ._._A :._rl..-r-‘-1 ..~-l:~..r:~~~ Qllcl IUULLI”II SLUU C” UCSll;” USCIllI p‘vcc”‘” I”1 lllCUlcisIl auLl 1‘1UU~Llla‘ apyllr;arl”1la. It should be possible to alter the substrate specificity and pH optimum of enzymes, to increase the thermal stability of proteins [l] and to design proteins that can be used in non-aqueous solvents. In addition to modifying existing proteins, it should be possible to design entirely novel peptides and proteins with useful properties. It is very difficult to predict the appropriate sequence changes however. We cannot foresee how a protein will fold and although the amino acid sequence of a protein determines its three-dimensional structure, knowledge of this sequence does not yet allow us to predict the structure [2]. The relationship between protein structure and function is only partially understood [3]. Genetic engineering affords us novel possibilities for under standing the molecular basis of interaction between an antibody and a protein antigen, in that the structures of the antibody, the protein epitope and the antibody protein complex can be defined. This will be beneficial for the further development of the immunoassay technologies at present widely used in clinical chemistry laboratories. Detailed investigations into the structure of the epitopes of the antigen will allow better characterization of the antibodies used in different assays.