title: Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets.
abstract: A dodecapeptide (γ400-411) derived from a fibrinogen γ-chain carboxyl-terminal sequence recognizes specifically the active form of GPIIb/IIIa on the surface of activated platelets. For the purpose of efficient hemostasis, we previously developed ADP-encapsulated liposomes modified with human-dodecapeptide (HHLGGAKQAGDV, human-H12). On the other hand, the amino-acid sequence of H12 from rats is HHMGGSKQVGDM, having only 67% homology to that from humans. Here, we investigated the ability of rat-H12 in comparison with human-H12 to bind to platelets. Firstly, rat platelets were activated with phorbol-12-myristate-13-acetate (PMA), and the activation was confirmed by flow cytometry. Next, we evaluated the dissociation constant (K(d)) of human-H12 and rat-H12 for dissociation from rat platelets by using FACS. As a result, the K(d) of human-H12 and rat-H12 with respect to rat platelets was 2.78 ± 0.21 and 2.91 ± 0.22 μM, respectively. Furthermore, H12 from both species inhibited quite similarly the aggregation of rat platelets in platelet-rich plasma (PRP). These results suggest that H12 from different species with different amino acid sequences interacts similarly with GPIIb/IIIa on platelets.
authors.affiliation: Pharmaceutical Research Department of CMC Research Center, Mitsubishi Tanabe Pharma Corporation, 3-16-89, Kashima, Yodogawa-ku, Osaka 532-8505, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tokutomi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tagawa
authors.forename: Maki
authors.initials: M
authors.lastname: Korenaga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Chiba
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Naohide
authors.initials: N
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Handa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C027539:fibrinopeptides gamma; D005340:Fibrinogen