Institute of Biostructures and Bioimaging, National Research Council, Naples, Italy.
Int J Nanomedicine. 2013;8:2555-65. doi: 10.2147/IJN.S44186. Epub 2013 Jul 22.
A genetically modified recombinant gH625-c-prune was prepared through conjugation of c-prune with gH625, a peptide encompassing 625-644 residues of the glycoprotein H of herpes simplex virus 1, which has been proved to possess the ability to carry cargo molecules across cell membranes. C-prune is the C-terminal domain of h-prune, overexpressed in breast, colorectal, and gastric cancers, interacting with multiple partners, and representing an ideal target for inhibition of cancer development. Its C-terminal domain results in an intrinsically disordered domain (IDD), and the peculiar properties of gH625 render it an optimal candidate to act as a carrier for this net negatively charged molecule by comparison with the positively charged TAT. A characterization of the recombinant gH625-c-prune fusion protein was conducted by biochemical, cellular biology and confocal microscopy means in comparison with TAT-c-prune. The results showed that the gH625-c-prune exhibited the ability to cross biomembranes, opening a new scenario on the use of gH625 as a novel multifunctional carrier.
一种基因修饰的重组 gH625-c-prune 通过 c-prune 与 gH625 的连接而制备，gH625 是包含单纯疱疹病毒 1 糖蛋白 H 的 625-644 个残基的肽，已被证明具有携带货物分子穿过细胞膜的能力。c-prune 是 h-prune 的 C 末端结构域，在乳腺癌、结直肠癌和胃癌中过表达，与多个伴侣相互作用，是抑制癌症发展的理想靶点。其 C 末端结构域导致固有无序结构域（ID），并且 gH625 的特殊性质使其成为比带正电荷的 TAT 更适合作为这种净负电荷分子载体的理想候选物。通过与 TAT-c-prune 进行比较，通过生化、细胞生物学和共聚焦显微镜手段对重组 gH625-c-prune 融合蛋白进行了表征。结果表明，gH625-c-prune 具有穿过生物膜的能力，为 gH625 作为新型多功能载体的应用开辟了新的前景。
