Peptide cell-display for selection of inhibitors against human glutathione transferase P1-1 (hGSTP1-1) allozymes

Abstract

We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme involved in MDR. We developed a combinatorial strategy aiming at designing peptide inhibitors against the hGSTP1-1 isoenzyme. We employed a combinatorial peptide library featuring engineered E. coli cells harboring a plasmid able to express a fusion protein containing random 12peptides. After five selection rounds, clones were screened for hGSTP1-1 binding (dot blot hybridization) 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 . The synthetic peptides were studied for their inhibition potency against three human GSTP1-1 allozymes, A, B and C