This PDF file includes:

• Section S1. Supplementary Materials and Methods
• Fig. S1. Identification of potential Aβ42 aggregation inhibitors using a bacterial genetic screen.
• Fig. S2. Identification of different cyclic peptide clusters appearing in the sorted population.
• Fig. S3. ΑβC7-1 and AβC7-14 inhibit the aggregation of Aβ42 in vitro.
• Fig. S4. ΑβC7-1 and AβC7-14 inhibit the aggregation of Aβ42 in vivo.
• Table S1. Deep sequencing analysis of the peptide-encoding regions of ~3.4 million clones from the constructed pSICLOPPS-NuX₁X₂X₃X₄X₅X₆ library.
• Table S2. Enrichment (blue) and depletion (red) of the 20 amino acids in each position of the heptapeptide sequences.
• Table S3. Distribution of the heptapeptide sequences in the different clusters identified.
• Table S4. Sequences and frequency of appearance of cluster I and cluster II heptapeptide sequences as determined by high-throughput sequencing of the enriched library after the seventh round of sorting.
• Table S5. Molecular properties of the selected cyclic heptapeptides AβC7-1 and AβC7-14 compared to those of conventional drugs, oral macrocyclic (MC) drugs, and nonoral MC drugs.
• Table S6. Plasmids and PCR primers used in this study.
• References (52, 53)

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