7] The use of carbodiimides in the preparation of immunizing conjugates

Abstract

Publisher Summary This chapter discusses the use of carbodiimides in the preparation of immunizing conjugates. Sheehan and Hess introduced the use of carbodiimides for the synthesis of peptide bonds. The preparative procedure is simple and easy to perform, and therefore it became the most important coupling method. It is postulated that an intermediate is formed that can react, either with an amine to give the desired peptide or to rearrange to an acyl urea. The acyl ureas are the main side products at elevated temperatures, and in order to shift the reaction toward peptide bond formation, temperatures around 0° should be used. Presence of an amino group, during the reaction, also reduces the formation of acyl urea. The most commonly used carbodiimide for peptide synthesis performed in organic solvents is dicyclohexylcarbodiimide. In the field of immunology, the main use of carbodiimides has been in the conjugation of weakly immunogenic or nonimmunogenic compounds to larger carder proteins or to synthetic antigens, thus enhancing their immunogenicity. Among the immunogens synthesized, there are complexes containing low molecular weight peptides, such as protein fragments or hormones, steroidal hormones, prostaglandins, cyclic nucleotides, and plant hormones.