Iodinated Diketopiperazines: Synthesis and Biological Evaluation of Iodinated Analogues of Cyclo(L‐Tyrosine‐L‐Tyrosine) Peptides

Abstract

We developed a simple strategy to diiodinated tyrosine (Tyr) amino acid at the 3‐ and 5‐ positions from the commercially available Fmoc/Boc‐L‐Tyrosine monomer. The iodinated tyrosine monomer have been further adopted to generate a variety of iodinated Fmoc tyrosine dimers. Upon Fmoc elimination, we obtained diketopiperazine (DKP) analogues of Cyclo(L‐Tyr‐L‐Tyr) with varied number of iodine atoms. We also report the biological studies of these iodinated DKP analogues in three different cancer cell lines. We demonstrate that the number of iodine atoms in the Cyclo(L‐Tyr‐L‐Tyr) DKP analogues, and the presence of electron‐rich phenolic group are essential structural parameters to have pronounced cytotoxic activity in three different cancer cell lines.

Structure‐based improvement of the binding affinity and recognition specificity of peptide competitors to target pediatric IL‐5R/IL‐5 interaction by gluing halogen bonds at their complex interface

“…Previously, halogenation strategy has been successfully used to confer and alter supramolecular behavior for peptides, 24 which, for example, was found to promote the self‐assembly of amyloidogenic peptides 25–28 and diphenylalanine peptides 29 through well‐organized halogen bonds. In addition, the halogen bonds have also been exploited as a powerful tool to modulate peptide conformation 30 and to improve the cytotoxic activity of peptides agents against cancer cells 31 . In this study, we demonstrated that although AF17121 can bind to IL‐5R in a good potency, the peptide exhibits a wide specificity and promiscuity toward the IL‐R family due to the high conservation of the family members in sequence, structure and function.…”

“…In addition, the halogen bonds have also been exploited as a powerful tool to modulate peptide conformation 30 and to improve the cytotoxic activity of peptides agents against cancer cells. 31 In this study, we demonstrated that although AF17121 can bind to IL-5R in a good potency, the peptide exhibits a wide specificity and promiscuity toward the IL-R family due to the high conservation of the family members in sequence, structure and function. We further improved the binding affinity of AF17121 to IL-5R and the recognition selectivity of AF17121 for IL-5R over other IL-Rs by gluing rationally designed halogen bonds at the protein-peptide complex interface.…”