Research for the anti-thrombus and anti-inflammation of annexin-V

胎盘抗凝蛋白- i （PAP-I， T.Funakoshi et al., Biochemistry 26,5572(1987)）是从人胎盘中纯化出来的Ca^<2+>依赖性磷脂结合蛋白的膜联蛋白家族成员。蛋白质和cDNA序列数据显示，pap - 1、II、III和IV分别对应于annexin-V、IV、III和II （M.J.Crumpton和j.r.d dedman, Nature 345, 212(1990)）。Annexin-V是这些蛋白中最丰富的，由319个氨基酸组成，每个氨基酸含有70-90个氨基酸的四个串联重复序列（T.Funakoshi et al., Biochemistry 26,8087(1987)）。膜联蛋白v抑制血液凝固的外在和内在途径，并在Ca^<2+>存在下特异性结合阴离子磷脂表面。膜联蛋白v也抑制磷脂酶A2对磷脂的水解。这种抑制作用被认为可以抑制前列腺素的合成，从而起到抗炎作用。肽SHLRKV和DHTLIR，分别对应于膜联蛋白v残基204-209和266-271，包含在膜联蛋白v的功能位点，并表现出有效的抗凝血活性，而丙氨酸取代组氨酸的肽则没有。此时，我们合成了这两种肽以及HDTLIR和HDTQPRVLD两种肽，以确定这些肽的结构和功能关系。这些肽和膜联蛋白- v分别降低了小鼠肺栓塞的死亡率。

Placental anticoagulant protein-I(PAP-I, T.Funakoshi et al., Biochemistry 26,5572(1987), purified from human placenta, is a member of annexin family of Ca^<2+>-dependent phospholipid binding proteins. Protein and cDNA sequence data show that PAP-I, II, III and IV correspond to annexin-V, IV, III and II, respectively (M.J.Crumpton and J.R.Dedman, Nature 345, 212(1990)). Annexin-V, the most abundant of these proteins, is composed of 319 amino acids containing four tandem repeats of 70-90 amino acid each (T.Funakoshi et al., Biochemistry 26,8087(1987)). Annexin-V inhibit the extrinsic and intrinsic pathways of blood coagulation and binds specifically to anionic phospholipid surfaces in the presence of Ca^<2+>. Annexin-V also inhibits the hydrolysis of phospholipid by phospholipase A2. This inhibition is thought to suppress prostaglandin synthesis leading to antiinflammatory action.The peptides, SHLRKV and DHTLIR, corresponding to annexin-V residues 204-209 and 266-271, respectively, are included in the functional site of annexin-V and exhibit a potent anticoagulant activity but the peptides in which alanine is substituted for histidine do not. At this time, we synthesized the both peptides and the other peptides, HDTLIR and HDTQPRVLD, to determine the relationship of the structures and function of these peptides. These peptides and annexin-V lowered the death rates of the pulmonary embolism in mice, respectively.