A series of tripeptides (Z-LLF-R) with various modifications at their C-terminus were synthesized and evaluated for their ability to prevent the activation of NF-κB through inhibition of IκB protease. Of the compounds evaluated only the C-terminal aldehydes 5a,b were active in our Jurkat T-cell based assay. Compound5a also decreased IL-2 and IL-8 levels in these cells indicating that inhibitors of IκB protease can have an effect on various signaling pathways.