Chemical Synthesis of Highly Functional Artificial Protein.

蛋白质-核酸相互作用是生命科学中非常重要的相互作用之一。从这一角度出发，选择鱼类精子中的鱼精蛋白等DNA结合蛋白作为本课题“高功能人工蛋白的化学合成”的主要靶蛋白。作为对鱼精蛋白功能的探讨，化学合成了(1)鱼精蛋白模型多肽，(2)鱼精蛋白二聚体和三聚体，(3)Pro取代鱼精蛋白类似物。对其类鱼精蛋白功能的研究表明，鱼精蛋白有一种特殊的DNA结合机制，其空间构象，例如转角结构参与其中。第二个靶标DNA结合蛋白-RNA聚合酶II的项目也启动了。此外，成功地合成了具有抑制恶性黑色素瘤转移作用的序列多肽，作为高功能人工蛋白的例子。

Protein-nucleic acid interaction is one of the very important ones among the various interactions in life science. From this standpoint, DNA-binding proteins, such as protamine in fish sperm, were chosen as the main target proteins of the present project, "Chemical synthesis of highly functional artificial protein". As approaches to the protamine function, (1)protamine-model peptides, (2)protamine dimer and trimer, (3)Pro-replaced protamine analogue were chemically synthesized. Investigations about their protamine-like functions suggested one special DNA-binding mechanism of protamine, in which its steric conformation, turn structure for example, participated.A project for the second target DNA-binding protein, RNA polymerase II, also started. In addition, sequential polypeptides which have inhibitory effect on the metastases of malignant melanoma were successfully synthesized as examples of highly functional artificial protein.