Identification of peptides targeting the surface of Plasmodium falciparum-infected erythrocytes using a phage display peptide library
Identification of peptides targeting the surface of Plasmodium falciparum-infected erythrocytes using a phage display peptide library
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DOI：
10.4269/ajtmh.2004.71.190
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发表时间：
2004-08-01
影响因子：
3.3
通讯作者：
Sherman, IW
中科院分区：
文献类型：
--
作者：
Eda, K;Eda, S;Sherman, IW
恶性疟原虫感染的红细胞 (iRBC) 质膜发生剧烈变化，使得 iRBC 的表面与未感染的红细胞的表面不同。为了鉴定能够特异性识别 iRBC 改变表面的小肽，我们在 iRBC 表面筛选了噬菌体展示肽库 (PDL)。 PDL 第六次淘选后，18 个测序克隆中的 8 个噬菌体克隆具有相同的序列 LVDAAAL（称为 PI），并且使用表达 P1 肽和合成 P1 肽的噬菌体证实了 P1 与 iRBC 表面的特异性结合。当P1肽与具有中等溶血活性的肽缀合时，肽缀合物以剂量依赖性方式抑制细胞内寄生虫的生长，而对照肽则没有效果。我们的结果表明，P1 肽可能是开发针对 iRBC 表面的抗疟疾药物的先导化合物。
Drastic changes in the plasma membrane of Plasmodium falciparum-infected red blood cells (iRBCs) make the surface of iRBCs distinct from that of the uninfected erythrocyte. To identify small peptides that would specifically recognize the altered surface of iRBCs, we screened a phage display peptide library (PDL) on the surface of iRBCs. After the sixth panning of the PDL, eight phage clones of 18 sequenced clones had the same sequence, LVDAAAL (named PI) and specific binding of P1 to the surface of iRBCs was confirmed using phage expressing P1 peptides and synthetic P1 peptide. When P1 peptide was conjugated with a peptide having moderate hemolytic activity, the peptide conjugate inhibited the growth of intracellular parasites in a dose-dependent manner, whereas control peptides were without effect. Our results demonstrate that the P1 peptide may be a lead compound for the development of anti-malarial agents targeting the surface of iRBCs.