【摘要】 趋化因子受体5(CCR5)是HIV-1与宿主细胞结合的辅助因子之一,其功能缺失或被CCR5拮抗剂封闭则会阻止HIV-1感染细胞.为得到与CCR5特异结合的肽类拮抗剂,采用噬菌体展示技术,以稳定表达CCR5的CHO细胞(CHO/CCR5)作为靶标,通过噬菌体随机12肽库筛选与CCR5特异结合的多肽;经过四轮筛选后,挑选20个阳性噬菌体克隆进行测序,从中得到11个含有AFDWTFVPSLIL序列的小分子肽.含该序列的噬菌体能与抗人CCR5单抗(2D7)竞争性结合CCR5,且合成肽AFDWTFVPSLIL对趋化因子RANTES与CHO/CCR5的结合具有明显的抑制作用,初步证明该小肽与CCR5具有特异性结合作用.更多还原

【Abstract】 Chemokine receptor-5 (CCR5) serves as a co-receptor necessary for the binding of HIV-1 to the host cells, the defective CCR5 function and the blocking of CCR5 sites by CCR5 antagonists will suppress the entry of HIV-1 to target cells. To acquire the peptide antagonists specifically binding CCR5, CHO cells stably expressing human CCR5 (CHO/CCR5) were used to select CCR5-binding peptides from a phage displayed 12-mer peptide library. After four rounds of selection, eleven out of the 20-phage clones shared the amino acid motif AFDWTFVPSLIL. The motif-containing phages could competitively bind to CHO/CCR5 cells with anti-human CCR5 mAb, and the synthetic peptide AFDWTFVPSLIL could inhibit RANTES binding to CHO/CCR5. These results suggest that the peptide could specifically bind CCR5 molecules.更多还原