Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Virology. 2012 Nov 25;433(2):308-19. doi: 10.1016/j.virol.2012.08.007. Epub 2012 Sep 7.
Feglymycin (FGM), a natural Streptomyces-derived 13mer peptide, consistently inhibits HIV replication in the lower μM range. FGM also inhibits HIV cell-to-cell transfer between HIV-infected T cells and uninfected CD4(+) T cells and the DC-SIGN-mediated viral transfer to CD4(+) T cells. FGM potently interacts with gp120 (X4 and R5) as determined by SPR analysis and shown to act as a gp120/CD4 binding inhibitor. Alanine-scan analysis showed an important role for l-aspartic acid at position 13 for its anti-HIV activity. In vitro generated FGM-resistant HIV-1 IIIB virus (HIV-1 IIIB(FGMres)) showed two unique mutations in gp120 at positions I153L and K457I. HIV-1 IIIB(FGMres) virus was equally susceptible to other viral binding/adsorption inhibitors with the exception of dextran sulfate (9-fold resistance) and cyclotriazadisulfonamide (>15-fold), two well-described compounds that interfere with HIV entry. In conclusion, FGM is a unique prototype lead peptide with potential for further development of more potent anti-HIV derivatives.
非格司亭（FGM）是一种天然来源于链霉菌的 13 肽，可在较低的微摩尔范围内持续抑制 HIV 的复制。FGM 还抑制 HIV 感染的 T 细胞与未感染的 CD4(+)T 细胞之间的细胞间转移，以及 DC-SIGN 介导的病毒向 CD4(+)T 细胞的转移。通过 SPR 分析确定 FGM 与 gp120（X4 和 R5）强烈相互作用，并证明其作为 gp120/CD4 结合抑制剂的作用。丙氨酸扫描分析显示，位置 13 的 l-天冬氨酸对于其抗 HIV 活性具有重要作用。体外产生的 FGM 耐药 HIV-1 IIIB 病毒（HIV-1 IIIB(FGMres)）在 gp120 位置 I153L 和 K457I 处显示出两个独特的突变。除了葡聚糖硫酸盐（9 倍耐药）和环三氮脒二磺酰胺（>15 倍）外，HIV-1 IIIB(FGMres)病毒对其他病毒结合/吸附抑制剂同样敏感，这两种都是干扰 HIV 进入的已知化合物。总之，FGM 是一种具有潜在进一步开发更有效的抗 HIV 衍生物的独特原型先导肽。
