趋化因子受体 CCR5 亲合短肽的筛选

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 .

Screening of Peptide Specific for Human Chemokine Receptor-5 From Phage Displayed Library

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.