Deprotection of the Fmoc protecting group was achieved by treatment with 5 mL of 20% (v/v) piperidine in DMF, for 10 min for 2 times. For the pteroic acid coupling, 2 eq of pteroic acid were suspended in 10 mL of DMSO and heated at 50 °C for 1 h. 8 eq of DIPEA and 2 eq of Pybop were added to the suspension, which was then reacted with the peptidyl-resin for 16 h at 40 °C. The pteroic acid coupling was then repeated for further 16 h at 40 °C. Cleavage from the resin was performed in TFA/H2O/TIS 95:2.5:2.5 solution for 2 h. The resin was removed by filtration and the filtrate concentrated by N2 flow. The crude product was precipitated with cold diethyl ether, centrifuged (4,000 g for 10 min) and the supernatant was discarded. The precipitate was dissolved in 2 mL of CH3CN + 0.1% TFA, diluted with 13 mL of H2O + 0.1% TFA, filtrated through a 0.22 µm syringe filter and purified by RP-HPLC. Lyophilization of the pure product fractions afforded the desired compound as a red powder, which was characterized by LC-MS (Supplementary Figure ). Cell viability assay MCF7 and HEK293 cells were seeded at a density of 2×10 4 cells per well in a Nunc™ MicroWell™ 96-well plate (Thermo Scientific, #10174221) and grown at 37 °C in a 5% CO2 atmosphere in DMEM supplemented with 10% (v/v) FBS for 24 h. KB cells were seeded at a density of 7×10 3 cells per well in a 96-well plate and grown at 37 °C in a 5% CO2 atmosphere in folic acid-depleted RPMI-1640 medium supplemented with 10% (v/v) FBS for 24 h. Stock solutions of compounds 3-7 and 9-11 were obtained by dissolving the compounds in sterile deionized water. Compounds 1, 2, 8, 12-15 were dissolved in pure DMSO. The stock solutions were diluted into the proper medium (according to the cell line tested) supplemented with 10% FBS to the appropriate concentration, and cells in each well were incubated with 100 µL of the solution. The solutions in each well were then adjusted to a concentration of 1% (v/v) DMSO. After 24 h at 37 °C, 20 µL of CellTiter-Blue™ (Promega, #G8080) was added to each well. The plate was incubated for another 4 h at 37 °C before analysis on a Perkin Elmer Victor X plate reader (excitation 531 nm; emission 595 nm). Each data point was calculated from a minimum of nine values resulting from three biological replicates (i.e., cells split from three different passages); each biological replicate is calculated from three technical replicates (i.e., cells split from the same passage). Value from media-only with CellTiter-Blue™ was set as 0% viability.