Design and synthesis of conformationally constrained, extended and reverse turn pseudopeptides as Grb2-SH2 domain antagonists

A series of conformationally constrained and flexible pseudopeptide derivatives of the tripeptide pYVN were prepared as potential antagonists of interactions of phosphotyrosine peptides with the Grb2-SH2 domain. The conformationally constrained compounds contained trans- and cis-cyclopropanes as replacements to enforce locally extended and reverse turn peptide conformations, respectively.