Fig. 4: High-diversity libraries facilitate discovery of p53-like peptides.
From: Ultra-large chemical libraries for the discovery of high-affinity peptide binders
a Design of libraries used in selections against MDM2. Each library was derived from the same batch of split-and-pool SPPS. The readout for selections was the number of sequences bearing the MDM2-binding motif, FXXXWXX(L/V). b Motif-containing sequences could be identified by selection from individual 2 × 108-member libraries (one-pot), but not from 2 × 107-member or 1 × 109-member libraries (obtained by pooling the five individual 2 × 108-member libraries; one-pot). Selections from the five individual 2 × 108-member libraries (multi-pot; 1 × 109 members total) identified five motif-containing sequences, suggesting that library size was enabling for identification of p53-like peptides as long as the mixture was not overly complex. Error bars correspond to one standard deviation among three technical replicates. c Sequences of known MDM2-binding peptides, including the native MDM2-binding epitope of p53 (residues 17–28) and three peptides identified from phage display, aligned with sequences identified from b. Known hot spot residues (F, W, L/V) are indicated in blue; aligned hot spot positions are indicated in bold and underline; and additional conserved residues are indicated in purple.
