Key Points
• Source: Acta Pharmaceutica Sinica B
• Conclusion/Relevance: “Our study demonstrates that the stapled peptide 3 exhibits a stable α-helical structure with improved affinity and stability, strong resistance to proteolysis, and enhanced biological activity. The stapled peptide 3 provides a practical approach for polypeptide drug research, particularly for studies of more in-depth design of peptidomimetics and non-peptide drugs. The future experiments will focus on optimizing the potency of peptide 3 by using the analysis of structure–activity relationships and advancing it to preclinical testing of peptide 3 in murine models of KRAS-driven cancers. Our discovery will encourage the development of novel drugs for inhibition of KRAS mutations.”
• Of note, peptide 3 has never before been investigated as an inhibitor of the proliferation of lung cancer cells. Peptides 1 and 3 were similar in proliferation inhibition in H358 cells.
• “Our study demonstrates that the stapled peptide 3 exhibits a stable α-helical structure with improved affinity and stability, strong resistance to proteolysis, and enhanced biological activity. The stapled peptide 3 provides a practical approach for polypeptide drug research, particularly for studies of more in-depth design of peptidomimetics and non-peptide drugs,” per the authors.
• Future research will aim to optimize the potency of peptide 3 via structure–activity relationships and moving toward preclinical testing of peptide 3 in murine models of KRAS. Drug discovery for KRAS has been very challenging, and this discovery is a move in the right direction, per the authors.
• Discussion question: What clinical potential do you think that stapled peptide 3 presents?