D-Retro-Inverso Peptide Candidates for Inhibiting SAA Cardiac Amyloidosis

In a recent study of a mice model it was suggested that after myocardial infarction Serum Amyloid A (SAA) aggregates are formed that contribute to the long-term complications of the infarct, and that a similar mechanism may exist for humans. Motivated by this hypothesis we have designed four peptide candidates that may interfere with formation of SAA3 fibrils, and using all-atom molecular dynamics have evaluated their ability to destabilize SAA fibrils. As the lifetime of peptide drugs can be increased by replacing L-amino acids with their mirror D-amino acids, we have built the peptides from D-amino acids. We identify two of these peptides, DRI-R5S and DRI-H6A, as promising drug candidates.