Peptide BRC3: Design, Synthesis And Its Interaction With Peptide P53(171-192)

Breast cancer has been influenced on the human health in recent years. The formation ofcancer involves that multiple genes and their products have been changed, these changes leadto the disorder of cell growth and differentiation mechanisms, which makes the cellhyperplasia is out of control and causes the cancer, Therefore, Conquering cancer has alwaysbeen a big problem in the medical field. With the advances of research on biochemistry andtechnology, new proto-oncogenes and tumor suppressor genes have been founding, includingRAD51and p53, which are widely studied. p53is an important tumor suppressor genes, theperformance of its protein function need the regulation of breast cancer susceptibility gene2(BRCA2) and its products. Therefore, p53(171-192) was the key peptide of p53protein,which was chose as the target, and the repeated motif BRC3in BRCA2was taken as thebreakthrough point, a series of BRC peptides were designed and synthesized. Moreover, theinteraction between the target peptide and BRC peptides were studied, whose aims atobtaining the BRC-like peptides that stronger interacted with p53target peptide, providing anew design concept and theoretical basis for the development of peptide drugs and thetreatment of cancer.In this thesis, the FMOC protection strategy, Wang resin as the carrier, the combine ofTBTU/HOBT/DIEA as coupling reagents were selected to synthesize peptide. p53(171-192)and series of BRC peptides as well as fragments KNIGVAKEG、FFDQKPE、FFQTASG、FETSDT were synthesized by solid phase peptide synthesis, purified by reversed-phaseHPLC and characterized by ESI-MS analyses.The interaction of BRC peptides and fragments with p53(171-192) had beeninvestigated by using CD spectra, according to the characteristic peak distribution of thesecondary structure, using the neural network algorithm and K2D fitting software, the contentof the alpha helix, beta folding, angle and random coil were calculated. The results obtainedindicated that BRC3-1showed the highest affinity for p53(171-192), compared with the otherBRC peptides. Meanwhile, the interaction of fragments FFQTASG and p53(171-192) was thestrongest in a series of peptide fragments, which was similar to BRC3. Therefore, weconcluded that fragment FFQTASG of BRC3was the most highly conserved sequence, and played an important role in the functions and interaction of BRC3.