additional control, yeast cells harboring large T and p53 were assayed in parallel under identical treatments and conditions. Found at: doi:10.1371/journal.pone.0011403.s004 (1.17 MB TIF) Figure S2 Structures of lysine derivatives of cyclic compounds Ia (A) and IIa (B). The two compounds were synthesized with a lysine residue covalently attached to their free amide groups, as described in Supporting Methods S1. Found at: doi:10.1371/journal.pone.0011403.s005 (0.26 MB TIF) Figure S3 Compound Ia does not inhibit Ubc4-dependent polyubiquitylation of proteasome-associated components. Com- ponents of the proteasome holoenzyme undergo K48-based polyubiquitylation in the presence of the ubiquitin ligase Hul5 and the E2 enzyme Ubc4 in a 1-h reaction. Compound Ia does not inhibit the formation of Ubc4-dependent high molecular weight ubiquitin adducts at any of the concentrations tested. DMSO denotes the addition of the solvent at the concentration equivalent to that added when using the maximum concentration of compound Ia used in this experiment (500 mM). Found at: doi:10.1371/journal.pone.0011403.s006 (1.42 MB TIF) Figure S4 Structures of fluoresceinated derivatives of cyclic compounds Ia (A) and IIa (B). The two compounds were synthesized with a fluoresceine isotiocyanate moiety covalently attached to their free amide groups, as described in Supporting Methods. Found at: doi:10.1371/journal.pone.0011403.s007 (0.40 MB TIF) Figure S5 Uptake by mammalian cells of fluoresceinated compounds Ia (Ia-FITC) and IIa (IIa-FITC). HeLa cells, grown on sterile coverslips, were incubated overnight with 100 mM of either Ia-FITC or IIa-FITC, and processed for immunocytochem- istry for detection of Ubc13. As a control, HeLa cells were incubated with unconjugated FITC. Found at: doi:10.1371/journal.pone.0011403.s008 (4.19 MB TIF) References 1. 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