A β-hairpin peptide with pH-controlled affinity for tumor cells

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Tumor microenvironment (TME) exhibits dysregulated pH.
• Targeted drug delivery to cancer cells remains a challenge.

Purpose of the Study:

• To design and characterize a pH-responsive peptide for enhanced tumor cell internalization.
• To investigate the structural transformation of the peptide in acidic conditions.

Main Methods:

• Design of a β-hairpin peptide with specific amino acid sequence.
• Assessment of peptide structural changes under varying pH conditions.
• Quantification of peptide internalization in tumor cells at different pH levels.

Main Results:

• The designed peptide (SSRFEWEFESS^DPRGDPSSRFEWEFESS) exhibits a pH-dependent conformational switch.
• Peptide transitions from a flexible linear form to a rigid loop structure in weakly acidic environments.
• Tumor cell internalization of the peptide significantly increases under weakly acidic conditions.

Conclusions:

• The pH-responsive peptide demonstrates potential for targeted cancer therapy.
• Structural changes in response to tumor acidity enhance cellular uptake.
• This peptide design offers a promising strategy for improving drug delivery efficiency in oncology.