Novel anticoagulant peptides from the functional site of human placental anticoagulant protein.

Histidine-containing peptides SHLRKV and DHTLIR, corresponding to placental anticoagulant protein-I (PAP-I) residues 204-209 and 266-271, respectively, are included in the functional site of PAP-I and exhibit anticoagulant activity, but the peptides in which alanine is substituted for histidine do not. However, the peptide KHALKG, corresponding to the region from Lys-97 to Gly-102, did not exhibit an anticoagulant activity, showing that it is not included in the functional site. These findings thus suggest that His-205 and His-267 are involved in the Ca(2+)- or the phospholipid-binding site of PAP-I but that His-98 is not.