Figure 4.

Selection of PrP binders from a DNA-encoded macrocycle library. A, enrichment plot of macrocycle DEL compounds versus input rank. *KRD series compounds (gray) are frequent hitters. B and C, structures of the DEL hits OCJS and CCTS synthesized off-DNA. DEL macrocycles are synthesized as stereoisomers on-DNA, so each cis/trans isomer pair was synthesized off-DNA for testing (c, cis; t, trans). (D and E) TROSY spectra of ¹⁵N-HuPrP90-231 with the cis- and trans-isomers (200 μm) of OJCS and CCTS.