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Replacement of the L-amino acids of 23 with D-amino acids were not productive (Andersson et al., 2010)

This approach is appealing, but it has not been proven in large human trials

In summary, both direct design relying on mechanistic knowledge and available structural data from the oxytocinase subfamily of M1 aminopeptidases as well as iterative manipulations of the parent peptide Ang IV, involving insertion of unnatural amino acids as -amino acids, macrocyclizations and various structural simplifications have provided highly potent selective Ang IV peptidemimetics inhibiting IRAP

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