Peptide Racemization

Amino acid racemization is one of the most detrimental side reactions in chemical peptide synthesis. It is known that biological activities of the peptide/protein molecules are directly correlated with their dimensional atomic alignments while the inversion of the configuration at certain peptide Cα chiral centers might cause the local spatial rearrangement of the critical functional groups. Besides, racemization of a single amino acid in a certain peptide chain could exert a significant impact on the overall conformation of the affected molecule. Both of these factors are capable of substantially influencing the biological activities of concerned peptide molecules. Taking the consequences of amino acid racemization into account it is understandably necessary to keep the chiralities of the assembled amino acids intact during the peptide chemical synthesis. Nevertheless, this norm is sometimes difficult to be complied with due to the intensive inclination of certain amino acids to undergo racemization predominantly at the step of the amino acid/peptide carboxylate activation. The mechanism of amino acid racemization, racemization-prone peptide synthesis, as well as solutions in an effort to alleviate racemization side reactions will be dedicatedly discussed in this chapter.