| Research Abstract |
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.
|
