Conformation-switchable helical polypeptide eliciting selective pro-apoptotic activity for cancer therapy

Stimuli-Responsive Polypeptides for Biomedical Applications

“…Among them, PABL3, a pH-triggered low-to-high helix, showed much higher calcein delivery effectiveness and also a pH-activated cell-penetrating property at pH 6, indicating that the pH-responsive helical formation contributed to selective cancer targeting [11] (Figure 3). For an advanced version of pH-responsive transformable polypeptides, they developed a novel polypeptide which was able to simultaneously achieve cancer targeting and therapy (Figure 3 and Figure 4) [12]. Likewise, the pH-responsive polypeptide RP4F was converted to a high helical formation at tumor pH because the electrostatic attractions within the side chains were diminished by the protonation of the anion-donating moieties (Figure 4a) [12].…”

“…For an advanced version of pH-responsive transformable polypeptides, they developed a novel polypeptide which was able to simultaneously achieve cancer targeting and therapy (Figure 3 and Figure 4) [12]. Likewise, the pH-responsive polypeptide RP4F was converted to a high helical formation at tumor pH because the electrostatic attractions within the side chains were diminished by the protonation of the anion-donating moieties (Figure 4a) [12]. Therefore, the pH-activated helical formation enabled the polypeptides to selectively penetrate the cancer cell membranes (Figure 4b) [12].…”

“…Likewise, the pH-responsive polypeptide RP4F was converted to a high helical formation at tumor pH because the electrostatic attractions within the side chains were diminished by the protonation of the anion-donating moieties (Figure 4a) [12]. Therefore, the pH-activated helical formation enabled the polypeptides to selectively penetrate the cancer cell membranes (Figure 4b) [12]. When RP4F was transformed to the high helix at low pH, the anion-donating groups became hydrophobic due to protonation, thereby forming the cationic amphipathic helix that can target and disrupt mitochondrial membranes (Figure 3 and Figure 4b) [12].…”

“…Therefore, the pH-activated helical formation enabled the polypeptides to selectively penetrate the cancer cell membranes (Figure 4b) [12]. When RP4F was transformed to the high helix at low pH, the anion-donating groups became hydrophobic due to protonation, thereby forming the cationic amphipathic helix that can target and disrupt mitochondrial membranes (Figure 3 and Figure 4b) [12]. The pH-activated helix targeted and then destabilized mitochondrial outer membranes, which created oxidative conditions [12].…”

“…In this review, we discuss the recent progress in stimuli-responsive polypeptide systems including pH, reduction, oxidation, glucose, adenosine triphosphate (ATP), and enzymes and elucidate the theoretical approaches for the past five years (Figure 1). For pH-responsive polypeptides, although they are prevalently exploited, several polypeptides possessing the property of conformational transitions via pH are mainly introduced in this review, which were very recently developed, and the future direction for the use of pH-responsiveness is suggested as well in this review (Figure 1) [10,11,12]. Additionally, the new stimuli-responsive characteristics, oxidation- and ATP-responsiveness, are covered in this review (Figure 1).…”