The Src-homology 2 (SH2) domains play an important role in protein-protein interaction, and are specific for the phosphotyrosine-containing peptides. Herein, we design and synthesis the phosphotyrosyl mimetic as a building block to set up the compound library using Fmoc solid phase peptide synthesis. And the library is composed of the phosphotyrosyl mimetic-containing tri- and tetrapeptides as SH2 domain inhibitors. In this library, the Grb2-SH2 domain preferably binds phosphotyrosyl peptides with the consensus sequence YXN, and the STAT-SH2 domain recognizes YXXQ tetrapeptides sequence. Additionally, in order to increase the scope of the library, we perform three different N-terminal modification in this peptides.