Effect of ribonucleases on the proliferation of K-562 cells. The incorporation of [methyl-3H]thymidine into cellular DNA was used to monitor the proliferation of K-562 cells in the presence of ribonucleases. Data points are the mean (± SE) from at least three separate experiments carried out in triplicate, and were fitted with eq 3. Values of IC50 are listed in Table 1. For dimeric and trimeric conjugates, the concentration is of the molecule, not the constitutive active sites. Each panel depicts a different theme; data for RNase A (○), G88R RNase A (□), and ONC (▽) are repeated for comparison. (A) Tethering within or outside of the RI-ribonuclease interface. (B) Analogous dimeric conjugates made with bis(maleimido)benzene linkers 4–6. (C) Analogous trimeric conjugates of RNase A (Z = +13), RNase 1 (Z = +19), and BS-RNase (Z = +28). (D) Trimeric conjugates of evasive monomers, or made with linker 7.