Certain glutathione S-transferase (GST) isoenzymes detoxify the cell from xenobiotics, thus becoming inhibition targets when overexpressed in various tumours leading to MDR. We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme involved in MDR. We employed a combinatorial peptide library featuring engineered E. coli cells harboring a plasmid able to express a fusion protein containing random 12 peptides which were inserted into the active loop of thioredoxin, which itself was inserted into the dispensable region of the flagellin gene. After five selection rounds, clones were screened for hGSTP1-1 binding and those with the strongest signal were selected and sequenced. Sequence alignments showed a core binding sequence which, along with selected peptide fragments, were synthesized using the solid phase methodology and Fmoc/tBu chemistry on 2-chlorotrityl chloride solid support. The four peptides were studied for their inhibition potency against hGSTP1-1 allozymes A, B and C
