Decoration of fibrinogen γ-chain peptide on adenosine diphosphate-encapsulated liposomes enhances binding of the liposomes to activated platelets.
For the purpose of efficient hemostasis, we previously developed ADP-encapsulated liposomes modified with a dodecapeptide (HHLGGAKQAGDV, H12), H12-(ADP)Lipo. This liposome actually enhanced platelet aggregation in vitro, and showed significant hemostatic effect in vivo. Since fibrinogen (Fbg) is abundant in the bloodstream, it is unclear why this liposome binds platelets so efficiently, overcoming the competition with Fbg. Therefore, we investigated the relationship between H12 density on the liposome and the binding ability to platelets, and evaluated the inhibitory effect of Fbg on the binding of H12-(ADP)Lipo to platelets. As a result, the binding ability to platelets steeply increased depending on H12 density until it reached about 3×10(15) H12 molecules/m(2). The 50% inhibition concentration of Fbg on the binding of H12-(ADP)Lipo to platelets was about 25-fold over the concentration of H12 molecules on the liposome. Moreover, almost no inhibition by Fbg was observed at the physiological concentration of it. This result suggests that the ability of H12 to bind to GPIIb/IIIa increased overwhelmingly by the anchoring to the liposome that enabled the cooperative binding of H12 peptides to the platelets.
Pharmaceutical Research Department of CMC Research Center, Mitsubishi Tanabe Pharma Corporation, 3-16-89, Kashima, Yodogawa-ku, Osaka 532-8505, Japan.
Koji
K
Tokutomi
Toshiaki
T
Tagawa
Maki
M
Korenaga
Masatoshi
M
Chiba
Tomohiro
T
Asai
Naohide
N
Watanabe
Shinji
S
Takeoka
Makoto
M
Handa
Yasuo
Y
Ikeda
Naoto
N
Oku
D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D001792:Blood Platelets / Q000378:metabolism*; D005340:Fibrinogen / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008081:Liposomes; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding
D008081:Liposomes; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C027539:fibrinopeptides gamma; D000244:Adenosine Diphosphate; D005340:Fibrinogen