TY - JOUR
T1 - Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets
AU - Tokutomi, Koji
AU - Tagawa, Toshiaki
AU - Korenaga, Maki
AU - Chiba, Masatoshi
AU - Asai, Tomohiro
AU - Watanabe, Naohide
AU - Takeoka, Shinji
AU - Handa, Makoto
AU - Ikeda, Yasuo
AU - Oku, Naoto
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/11/15
Y1 - 2012/11/15
N2 - 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 (Kd) of human-H12 and rat-H12 for dissociation from rat platelets by using FACS. As a result, the Kd 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.
AB - 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 (Kd) of human-H12 and rat-H12 for dissociation from rat platelets by using FACS. As a result, the Kd 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.
KW - Dodecapeptide
KW - Fibrinogen
KW - GPIIb/IIIa
KW - Hemostasis
KW - Human
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=84867401098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867401098&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2012.09.016
DO - 10.1016/j.ijpharm.2012.09.016
M3 - Article
C2 - 22985603
AN - SCOPUS:84867401098
SN - 0378-5173
VL - 438
SP - 296
EP - 301
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -