Peptide aptamers targeting mutant p53 induce apoptosis in tumor cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Mutations in the p53 tumor suppressor gene are common in cancers.
• Mutant p53 proteins gain new functions that promote tumor progression and aggressive phenotypes.
• Targeting mutant p53 offers a potential therapeutic strategy for cancer treatment.

Purpose of the Study:

• To isolate and characterize peptide aptamers (PAs) that specifically bind to mutant p53.
• To evaluate the efficacy of these PAs in inhibiting mutant p53's oncogenic functions.
• To explore the potential of PAs as a novel therapeutic approach for mutant p53-driven cancers.

Main Methods:

• Isolation of peptide aptamers (PAs) with high affinity for conformational mutants of p53.
• Molecular modeling to characterize the interaction between mutant p53 and PAs.
• Transient expression of PAs in cancer cells to assess their functional impact.

Main Results:

• Peptide aptamers (PAs) were identified that preferentially bind to mutant p53 over wild-type p53.
• Molecular modeling confirmed the specific interaction between PAs and mutant p53.
• Transient PA expression reduced mutant p53 transactivation activity and induced apoptosis in mutant p53-expressing cells.

Conclusions:

• Peptide aptamers (PAs) can specifically target and inhibit the oncogenic functions of mutant p53.
• These PAs represent a promising strategy for developing novel cancer therapies.
• Further development of PAs could lead to improved treatments for cancers harboring p53 mutations.