The use of synthetic peptides as immunogens has proved to be an important route for the production of antibodies to previously uncharacterised proteins. Once the oligonucleotide sequence of a gene has been determined the amino acid sequence of any protein encoded by that gene may be predicted. Peptides selected from such a sequence may then be used to raise antibodies that may prove cross-reactive with the native protein. Many antibodies to proteins have been raised for the first time using this approach.
The synthetic peptide approach to antibody production has several advantages over other methods. For example, the antibodies may be raised to specific areas of a protein in order to probe biochemical function or to block normal biological activity. It is also possible to raise antibodies to peptides from regions where the sequences are conserved between members of a family of closely related proteins so as to produce pan-reactive reagents. Conversely, antibodies specific to individual members of protein families may be generated by careful selection of unique amino acid sequences.
However, the use of peptides as antigens has two problems. Firstly, in contrast to proteins, small peptides themselves do not usually produce good antigenic responses. This can be overcome by attaching the peptide to a large carrier protein or by synthesizing a multiple antigenic peptide before immunization. Secondly, how do we select an appropriate peptide antigen from the protein sequence which will induce a population of antibodies that can bind to the native protein?