Inhibition of the aggregation of transthyretin by specific binding of peptides to aggregation-driving segments

A method for reducing or inhibiting transthyretin (SEQ ID NO:

• 1) aggregation, comprising contacting transthyretin amyloid fibrils with at least one peptide comprising the sequence:
• (SEQ ID NO:
• 2)
• PFHEHAEVVFTA;
• (SEQ ID NO:
• 3)
• PYSYSTTAVVTN;
• (SEQ ID NO:
• 4)
• HVAHPFVEFTE;
• (SEQ ID NO:
• 5)
• SYVTNPTSYAVT;
• (SEQ ID NO:
• 6)
• HFEVAFPVEHAT;
• (SEQ ID NO:
• 7)
• YVSNPTSTYVAT;
• or
• (SEQ ID NO:
• 8)
• VANTSPTSYYVT;
• wherein:
• at least one of the amino acids in the at least one peptide comprises an amino acid comprising a N-methyl group moiety;
• and/or
• the at least one peptide is coupled to a heterologous peptide tag comprising a plurality of arginine (R) amino acids;
• in an amount sufficient to reduce or inhibit transthyretin aggregation, so that transthyretin (SEQ ID NO:
• 1) aggregation is reduced or inhibited.

A method of observing the presence or absence of transthyretin amyloid fibrils in a biological sample comprising:

• (a) combining a biological sample with a peptide having the sequence:
• (SEQ ID NO:
• 2)
• PFHEHAEVVFTA;
• (SEQ ID NO:
• 3)
• PYSYSTTAVVTN;
• (SEQ ID NO:
• 4)
• HVAHPFVEFTE;
• (SEQ ID NO:
• 5)
• SYVTNPTSYAVT;
• (SEQ ID NO:
• 6)
• HFEVAFPVEHAT;
• (SEQ ID NO:
• 7)
• YVSNPTSTYVAT;
• or
• (SEQ ID NO:
• 8)
• VANTSPTSYYVT
• (b) allowing the peptide to bind to transthyretin amyloid fibrils that may be present in the biological sample;
• and
• monitoring combination (b) for the presence of complexes formed between transthyretin amyloid fibrils and the peptide;
• wherein the presence of said complexes show the presence of transthyretin amyloid fibrils in the biological sample.