Fig. 3: Synthetic d-proteins display similar bioactivity to their synthetic l- and recombinant counterparts.

Binding data for five synthetic protein targets to peptide ligands of the appropriate chirality are shown. Experimental details are outlined in the Supplementary Information Sections 1.7–1.12. A Synthetic d, l and recombinant BCL11a bind a model DNA oligonucleotide of the γ-globulin promoter⁵⁶ measured as an increase in FRET efficiency between FAM and terbium streptavidin. The same method was used to measure binding for the studies in (B, E, F, I). B Synthetic d, l and recombinant CHIP bind a peptide model of the heat shock protein 70 (Hsp70) C-terminus. C Synthetic d, l and recombinant IRAK2 display similar proportions of secondary structure by circular dichroism (CD) spectra recorded from 195 to 260 nm at 0.1 mg/mL. D Synthetic l, d and recombinant IRAK2 have similar melting temperatures (T_m) determined by variable temperature CD monitored at 222 nm from 20 °C to 100 °C in 5 °C steps. E Synthetic d, l and recombinant Max-Max bind a model DNA oligonucleotide of E-box DNA⁴⁷. F Synthetic d, l and recombinant Myc-Max bind a model DNA oligonucleotide of E-box DNA⁴⁸. G Synthetic d, l and recombinant ERG display similar proportions of secondary structure by CD spectra recorded as described in (C). H Synthetic l, d and recombinant ERG have similar melting temperatures determined as described in (D). I Synthetic d, l and recombinant MDM2 bind a p53-derived model peptide. For studies described in (A, B, E, F, I), the chirality of the binder was adjusted to that of the protein. J, K Synthetic l- and d-barnase selectively catalyze the hydrolysis of a stereochemically matched RNA substrate. Catalytic activity was measured as an increase in fluorescence intensity (see SI Section 1.11). No cleavage for the mismatched substrate pairs (l-RNA to l-barnase and d-RNA to d-barnase) was observed. The data in (A, B, E, F, I, J, K) are presented as mean ± SD, n = 2 technical replicates. L Experimentally determined biophysical and biochemical parameters. The reported values are based on the data presented in Supplementary Tables 1–6 and are obtained by applying the corresponding fitting models described in the Supplementary Information Sections 1.7–1.12 (n.d. = not determined).