Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwave assisted solid-phase synthesis method, in order to make a search for potential inhibitors for angiotensin I-converting enzyme(ACE) with minimum side effects in the treatment of hypertension. One peptide with the sequence Leu-Arg-Pro-Phe-Phe shows the strongest inhibition towards ACE with an IC50 value of 0.26 μmol/L in vitro. The study of structure-activity relationship shows that the introduction of a bulky group into the N-terminal of this series of inhibitors may enlarge steric hindrance, resulting in the poor inhibitory activity towards ACE. The inhibitory activity decreased in turn when L-Pro, D-Pro or Ac6c was at the C-terminal respectively. The binding interaction between each of these inhibitors and testicular ACE(tACE) was performed by molecular docking. The results suggest that Leu-Arg-Pro-Phe-Phe mainly occupied the S1 subsite of tACE, and made contact with tACE via seven H-bonds. It appeared that the site on the peptide that bound with tACE was influenced by the configuration of the amino acid, L or D-form, at the C-terminal of the peptide. Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwave assisted solid-phase synthesis method, in order to make search for potential inhibitors for angiotensin I-converting enzyme (ACE) with minimum side effects in the treatment of hypertension. One study with the sequence Leu-Arg-Pro-Phe-Phe shows the strongest inhibition toward ACE with an IC50 value of 0.26 μmol / L in vitro. The study of structure-activity relationship shows that the introduction of a bulky group into the N-terminal of this series of inhibitors may enlarge steric hindrance, resulting in the poor inhibitory activity towards ACE. The inhibitory activity decreased in turn when L-Pro, D-Pro or Ac6c was at the C- The binding suggest between each of these inhibitors and testicular ACE (tACE) was performed by molecular docking. The results suggest that Leu-Arg-Pro-Phe-Phe mainly occupies the S1 subsite of tACE, and made contact with tACE via seven Hb onds. It has that the site on the peptide that bound with tACE was influenced by the configuration of the amino acid, L or D-form, at the C-terminal of the peptide.