RESUMEN
Objective: To design and synthesize APC/Asef peptide inhibitors and investigate the structure-activity relationship between peptides inhibitors and APC protein for exploring better inhibitors. Methods: Based on the best-class inhibitor we had found before-MAI-400, eleven peptide inhibitors were designed, which included the changes of N-terminal capping group, the first amino acid Ala, the fifth amino acid Leu and the last amino acid Glu. According to the results of fluorescence polarization activity detection system and molecular docking, the structure-activity relationship of peptide inhibitors was investigated. Results: Among the eleven peptides, MPI-11 had the highest affinity, whose half maximal inhibitory concentration (IC50) was 0.973 1 mmol/L. The capping group of peptide N-terminal with tert-butoxycarbonyl group reduced the activity slightly. The substitution of the Ala caused different results, changing into Trp, His and Thr definitely reduced the activity but the substitution by Tyr or Phe did not influence the activity too much. And introducing benzene ring into the side chain of Leu had few effects on activity improving. The substitution of side chain carboxyl for amide at the C-terminal glutamate had little effect on the activity. Conclusion: Among the eleven peptides, the capping group of peptide N-terminal cannot be substituted into small groups and Ala cannot be substituted into other amino acids.
RESUMEN
BACKGROUND AND OBJECTIVES: beta-catenin has an essential role in intercellular adhesion and signal transduction. The Adenomatous poliposis coli (APC) protein interacts with beta-catenin in a multi-protein complex to regulate the level of expression of beta-catenin. Mutations in beta-catenin or APC gene can lead to the accumulation of beta-catenin in the cytosol and the nucleus. This study was designed to investigate the expression of APC and beta-catenin in laryngeal cancer. SUBJECTS AND METHOD: Immunohistochemical methods were used to determine the beta-catenin and APC protein expression in 15 laryngeal cancers. Results were correlated with clinicopathological parameters. RESULTS: beta-catenin expression to the plasma membrane was reduced or absent in 11 of 15 cases (73%) of the laryngeal cancers. Cytoplasmic expression of the beta-catenin was seen in 6 out of 15 cases (40%). APC immunoactivity was negative in 5 of 15 (33%) of the laryngeal cancers. One of the six cytoplasmic expressions of the beta-catenin was negative for APC immunoactivity, and one of the five negative for APC immunoactivity was cytoplasmic expression of the beta-catenin. CONCLUSION: There was no correlation between beta-catenin and APC protein in the analysis. This finding suggests that cytoplasmic expression of the beta-catenin resulted not from the APC mutation but from the beta-catenin mutation and abnormal Wnt signal. Only the expression of the beta-catenin in cytoplasm was associated with lymph node metastasis.