Studies On Synthesis And Properties Of BRC4-like And BRC7-like Peptides

Breast cancer is becoming one of the common female malignant tumors.BRCA2, an important cancer suppressor gene, plays an important role in the processof DNA repairing. P53is an apoptosis-inducing protein, which can inhibit theproliferation of tumor cells. There has eight Sequence (BRC1-BRC8) in theimportant functional areas BRCA2. The function P53can be controlled by theinteraction of BRCA2and P53. This progress can inhebit the occurance of breastcancer. Therefore, on the basis of the known consensus sequence, the BRC repeatprimitives were repeated structural transformation, which was important for theoccurrence Mechanism research of breast cancer and provided the theory foundationfor the P53peptide drug design.In this research，the P53（117-142）was selected as the target peptide,According to the structure characteristics of BRCA2,-------F-TASGK-(I/V)-(I/V)S---L-K----(L/F)-(D/E)---three analog peptide，the analog peptide BRC4(BRC4-1)and two analog peptides BRC7(BRC7-1, BRC7-2) were designed. These peptideswere synththesized by the method of Fmoc solid-phases, These peptides wereisolated and purified by RP-HPLC and characterized by ESI-MS.The purity of thepetides was more than90%.The interaction of BRC4，BRC4-1,BRC7-1and BRC7-2with P53（117-142）had been investigated by circular dichroism spectra. The result showed that Structuremodification to analong BRC affected the P53of secondary structure. The alphahelix proprotion of P53rised, but the beta fold proportion significantly increased,followed by a gradual decline with adding BRC4. When leu of BRC4was replacedby Trp, BRC4-1made the alpha helix proprotion and beta fold proportion of P53increased. While Ser was replaced by Cys, BRC7-1made the alpha helix proprotionof P53rised significantly. Adding BRC7-2which Thr, Val were replaced by Ser, Alamakes P53declined after an initial increase, and finally stabilized. By contrast, thebeta fold proportion increased slightly after Lower than the first. Showing that changing certain amino acid sites of BRC4and BRC7makes different to thesecondary structure of P53.