Modulating Transthyretin Fibril Stability with D-Retro-Inverso Peptides

<jats:p>A major cause of heart failure in elderly patients are deposits of Transthyretin (TTR) fibrils. Using molecular dynamic simulations, we explore how the stability of TTR fibrils can be modulated by D-Retro-Inverso (DRI) Peptides, built from D-amino acids with the sequence of the parent peptide switched, and describe a mechanism by which one of these peptides, DRI-K6V, disrupts TTR fibrils. Our results may open the way to design of peptide drugs targeting established TTR amyloidosis</jats:p>