Altering the local structure of the peptide, although introducing some degree of conformational bias, produces minimal modifications to the original peptide. Such modifications are generally limited to single amino acids and can be divided into local modifications to the backbone and side chains. Changes in single amino acids have been reported to cause extensive changes in peptide structure, such as substitution of carbonyl groups with thiol, methylene, phosphinic and boronic acid groups. The use of unnatural amino acids as building blocks for the development of peptidomimetics has now attracted extensive research interest. Local modifications of peptidomimetics can include α-amino acids bearing modified side chains, rigid cyclic compounds that are isosteres of amino acids, and so on.