Evaluation of Cyclic Peptide Inhibitors of the Grb7 Breast Cancer Target: Small Change in Cargo Results in Large Change in Cellular Activity

• Published in: Molecules Vol. 24; no. 20; p. 3739
• Main Authors: Sang, Jianrong, Kulkarni, Ketav, Watson, Gabrielle M., Ma, Xiuquan, Craik, David J., Henriques, Sónia T., Poth, Aaron G., Benfield, Aurélie H., Wilce, Jacqueline A.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.10.2019; MDPI
• Subjects: 1313 Molecular Medicine; 1601 Chemistry (miscellaneous); 1602 Analytical Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 3002 Drug Discovery; 3003 Pharmaceutical Science; Adapter proteins; Amino Acid Sequence; Amino acids; Antineoplastic Agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Bicyclic peptide; Binding Sites; Breast cancer; cancer cell migration; Cell adhesion & migration; Cell growth; Cell Line; Cell Line, Tumor; Cell Membrane Permeability; Cell Movement; Cell Movement - drug effects; Cell penetrating peptide; Cell Proliferation; Cell Proliferation - drug effects; Epithelial Cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Extracellular Signal-Regulated MAP Kinases; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Gene Expression Regulation, Neoplastic; grb7; GRB7 Adaptor Protein; GRB7 Adaptor Protein - antagonists & inhibitors; GRB7 Adaptor Protein - genetics; GRB7 Adaptor Protein - metabolism; Humans; inhibitor binding; Invasion; Investigations; Kinases; Ligands; lipid bilayer interactions; Lipid Bilayers; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Mass spectrometry; Mass spectrometry quantification; Organic chemistry; Peptides; Peptides, Cyclic; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - pharmacology; Phosphatidylcholines; Phosphatidylcholines - chemistry; Phosphatidylcholines - metabolism; Phosphatidylserines; Phosphatidylserines - chemistry; Phosphatidylserines - metabolism; Proliferation; Protein Binding; Protein Binding - drug effects; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; QD241-441; Scientific imaging; SH2-domain; Signal Transduction; Signal Transduction - drug effects; Signal Transduction - genetics; src Homology Domains; src Homology Domains - drug effects; Structure-Activity Relationship; Grb7; SH2-domain; inhibitor binding; invasion; proliferation; cell penetrating peptide; bicyclic peptide; cancer cell migration; lipid bilayer interactions; mass spectrometry quantification

Grb7 is an adapter protein, overexpressed in HER2+ve breast and other cancers, and identified as a therapeutic target. Grb7 promotes both proliferative and migratory cellular pathways through interaction of its SH2 domain with upstream binding partners including HER2, SHC, and FAK. Here we present t...