Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7

• Published in: Scientific reports Vol. 6; no. 1; p. 27060
• Main Authors: Gunzburg, Menachem J., Kulkarni, Ketav, Watson, Gabrielle M., Ambaye, Nigus D., Del Borgo, Mark P., Brandt, Rebecca, Pero, Stephanie C., Perlmutter, Patrick, Wilce, Matthew C. J., Wilce, Jacqueline A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2016; Nature Publishing Group
• Subjects: 631/535/1266; 631/92/611; 639/638/549/978; 82/80; 82/83; Affinity; Amino Acid Sequence; Breast cancer; Crystal structure; Crystallography, X-Ray; Drug Design; Drug development; ErbB-2 protein; Grb2 protein; GRB7 Adaptor Protein - antagonists & inhibitors; GRB7 Adaptor Protein - chemistry; Humanities and Social Sciences; Humans; Hydrogen Bonding; Models, Molecular; multidisciplinary; Peptide inhibitors; Peptides; Peptides, Cyclic - chemistry; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Science

The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we...