Yanoshita R, Iwasaki E, Kambe T, Samejima Y
Institute of Medicinal Chemistry, Hoshi University, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Biol Pharm Bull. 2000 Nov;23(11):1379-81. doi: 10.1248/bpb.23.1379.
Blomhotin is a novel peptide (pGlu1-Gly2-Arg3-Pro4-Pro5-Gly6-Pro7-Pro8-Ile9-Pro10-Arg11) which has been isolated from the venom of Agkistrodon halys blomhoffii and exhibits contractile activity on rat stomach fundus. We carried out a structure-activity study of blomhotin and its related peptides, and the findings suggested that the N-terminal portion of blomhotin is mainly responsible for affinity for the blomhotin receptor, whereas the C-terminal portion of blomhotin, Pro-Ile-Pro-Arg, is responsible for complete activation of the blomhotin receptor in the rat stomach fundus. In particular, the amino acids at positions 9 and 11 of blomhotin appear to be essential for binding and intrinsic activity. Using knowledge gained from this structure-activity analysis, we have identified photoactive blomhotin analogues that have sufficient biological activity to probe the target molecule of blomhotin.
竹叶青毒素是一种新型肽（焦谷氨酸1 - 甘氨酸2 - 精氨酸3 - 脯氨酸4 - 脯氨酸5 - 甘氨酸6 - 脯氨酸7 - 脯氨酸8 - 异亮氨酸9 - 脯氨酸10 - 精氨酸11），它是从日本蝮蛇的毒液中分离出来的，对大鼠胃底具有收缩活性。我们对竹叶青毒素及其相关肽进行了构效关系研究，结果表明，竹叶青毒素的N端部分主要负责与竹叶青毒素受体的亲和力，而竹叶青毒素的C端部分，脯氨酸 - 异亮氨酸 - 脯氨酸 - 精氨酸，负责大鼠胃底中竹叶青毒素受体的完全激活。特别是，竹叶青毒素第9位和第11位的氨基酸似乎对结合和内在活性至关重要。利用从这种构效关系分析中获得的知识，我们鉴定出了具有足够生物活性以探测竹叶青毒素靶分子的光活性竹叶青毒素类似物。
