Development of membrane‐active peptide therapeutics in oncology

Abstract

Membrane-active peptides play an essential role in many living organisms and their immune systems and counter many infectious diseases. Many have dual or multiple mechanisms and can synergize with other molecules, like peptides, proteins, and small molecules. Although membrane-active peptides have been intensively studied in the past decades and more than 3500 sequences have been identified, only a few received approvals from the US Food and Drug Administration. In this review, we investigated all the peptide therapeutics that have entered the market or were subjected to preclinical and clinical studies to understand how they succeeded. With technological advancement (e.g., chemical modifications and pharmaceutical formulations) and a better understanding of the mechanism of action and the potential targets, we found at least five membrane-active peptide drugs that have entered preclinical/clinical phases and show promising results for cancer treatment. We summarized our findings in this review and provided insights into membrane-active anticancer peptide therapeutics.

Purification, Conformational Analysis and Cytotoxic Activities of Host-Defense Peptides from the Giant Gladiator Treefrog Boana boans (Hylidae: Hylinae)

“…Each peptide is associated with an extended hydrophobic domain, comprising multiple Leu and Val residues on one face of the helix, that enables binding to (phospho)lipids in the bacterial cell membrane and a hydrophilic domain on the opposite face, containing multiple Lys residues, that promotes loss of integrity of the membrane [27]. The ability of figainin 2BN to produce death of non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells and colorectal adenocarcinoma HT-29 cells during a 24 h incubation at relatively low concentrations (LC50 values in the range 7 to 14 µM) suggests that the peptide may represent a template for the design of anti-cancer drugs, particularly when the tumor is not responsive to conventional pharmaceutical agents [28]. Previous studies from the laboratory have shown that loss of cell viability produced by cytotoxic frog skin peptides under the conditions of the present study is rapid [29], suggesting that the mechanism of action involves non-specific destruction of the integrity of the plasma membrane rather than induction of apoptosis.…”