Results of library selections against human tankyrase-1 (TNKS1). (a) Selection fingerprint, reavealing a preferential enrichment of compounds with A4 and B101. (b) Plot of sequence counts for library members, featuring B101 as preferred building block. The plot reveals a preferential enrichment of library members with linker A4 and building blocks C491, C453, C369, C183 and C182. The structures of the four most enriched compounds is shown in panel (c). The BIAcore profiles at various concentrations of ligand for the amide derivatives of A4/B101/C491, A3/B101/C491 and A5/B101/C491 are shown in panels (d), (e) and (f). Fitting of the sensograms for A4/B101/C491 in panel (d) yielded a koff = (2.1±0.8) x 10-3 s-1 and a kon = (1.7±0.2) x 105 s-1M-1, corresponding to a Kd = 15±8 nM.