“…In fact, today, the majority of DELs are encoded with dsDNA tags. Although having been used in early studies, , DELs encoded with single-stranded DNAs (ssDELs) are less abundant and they are often prepared with special encoding methods, such as DNA-templated synthesis (DTS), DNA routing, and DNA-directed assembly. , ssDNAs can also be used to assemble the encoded self-assembling chemical (ESAC) libraries − and DNA-encoded dynamic libraries. − Moreover, ssDELs are amendable to a number of selection methods suitable for nonimmobilized proteins, such as the interaction determination using unpurified proteins (IDUP), , the cross-linking-based methods, − and the selections against membrane proteins on/inside live cells (Figure c). , In these methods, the ssDNA tag provides a site for hybridization with an additional DNA to covalently connect with the target upon binding. These methods may expand the target scope of DELs to more complex targets in a more biologically relevant environment. , In addition, a recent report showed that ssDELs had higher enrichment folds than dsDELs, especially for low- to moderate-affinity binders .…”