Tjin Tham Sjin Robert M, Satchi-Fainaro Ronit, Birsner Amy E, Ramanujam V M Sadagopa, Folkman Judah, Javaherian Kashi
Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 2005 May 1;65(9):3656-63. doi: 10.1158/0008-5472.CAN-04-1833.
The first recombinant endostatin that elicited strong antitumor activity was expressed in Escherichia coli and administered as a suspension. Under these conditions, the protein retained its full antiangiogenic activity. Lack of requirement for a folded structure prompted us to investigate antitumor properties of synthetic peptides corresponding to different regions of endostatin. Here, we show that the entire antitumor, antimigration, and antipermeability activities of endostatin are mimicked by a 27-amino-acid peptide corresponding to the NH2-terminal domain of endostatin. This peptide contains three histidines that are responsible for zinc binding. Mutations of the zinc-binding histidines abolished its antitumor and antimigration activities, but not antipermeability properties.
首个引发强大抗肿瘤活性的重组内皮抑素在大肠杆菌中表达，并以悬浮液形式给药。在这些条件下，该蛋白质保留了其全部抗血管生成活性。由于对折叠结构没有要求，我们开始研究与内皮抑素不同区域相对应的合成肽的抗肿瘤特性。在此，我们表明，一种对应于内皮抑素NH2末端结构域的27个氨基酸的肽模拟了内皮抑素的全部抗肿瘤、抗迁移和抗通透性活性。该肽含有三个负责锌结合的组氨酸。锌结合组氨酸的突变消除了其抗肿瘤和抗迁移活性，但没有消除抗通透性特性。
