Selective apoptosis-inducing activity of synthetic hydrocarbon-stapled SOS1 helix with d-amino acids in H358 cancer cells expressing KRASG12C

Apoptosis-inducing activity of synthetic hydrocarbon-stapled peptides in H358 cancer cells expressing KRASG12C

“…Generally, the higher the α -helicity of the peptide, the higher the affinity for the KRAS G12C protein. Although the affinity of the stapled peptide 3 to KRAS G12C protein is higher compared with the positive peptide 1 , it is not as strong as peptide 5 obtained by the d -type amino acid substitution we reported previously 38 .…”

“…Biolayer interferometry experiments were performed according to our previous experimental methods 38 . The binding kinetic constants of stapled peptides to KRAS G12C protein were performed by ForteBio Octet RED 96 system.…”

A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography

“…[14][15][16][17] Incorporation of one or two D-residues in an α-helical L-peptide sometimes preserves helicity, as recently documented by X-ray crystallography for a macrocyclic peptide inhibitor of the p53-MDM2 interaction, 18 and by CD-spectroscopy in a stapled bicyclic peptide inhibitor of the EGF-EGFR complex 19 and a stapled peptide KRAS inhibitor. 20 Note that mixed chirality 10/12 helices have been reported for β-peptides. 21 For the case of antimicrobial peptides (AMPs), which are considered as an opportunity to address the public health threat of ESKAPE pathogens due to their ability to kill multidrug-resistant bacteria, [22][23][24][25][26] studies with short amphiphilic α-helical sequences have shown that mixed chirality analogs lose the ability to form α-helices, but often retain their antimicrobial activity while hemolysis and protease sensitivity are reduced.…”

“… 14–17 Incorporation of one or two d -residues in an α-helical l -peptide sometimes preserves helicity, as recently documented by X-ray crystallography for a macrocyclic peptide inhibitor of the p53–MDM2 interaction, 18 and by CD-spectroscopy in a stapled bicyclic peptide inhibitor of the EGF–EGFR complex 19 and a stapled peptide KRAS inhibitor. 20 Note that mixed chirality 10/12 helices have been reported for β-peptides. 21 …”

The Research Progress of Direct KRAS G12C Mutation Inhibitors

“…Another strategy is to prevent KRAS from combining with GEFs, which leads to the activation of KRAS. For example, Burns MC et al [ 7 ] found a small molecule that can combine with SOS1, which provided a basis for Xu L et al [ 8 ] to find related inhibitors. The third strategy is to change the location of the KRAS protein.…”