Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets

Koji Tokutomi, Toshiaki Tagawa, Maki Korenaga, Masatoshi Chiba, Tomohiro Asai, Naohide Watanabe, Shinji Takeoka, Makoto Handa, Yasuo Ikeda, Naoto Oku

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)296-301
Number of pages6
JournalInternational Journal of Pharmaceutics
Volume438
Issue number1-2
DOIs
Publication statusPublished - 2012 Nov 15

Fingerprint

Fibrinogen
Blood Platelets
Amino Acid Sequence
Platelet-Rich Plasma
Hemostasis
Platelet Aggregation
Liposomes
Adenosine Diphosphate
Flow Cytometry
Acetates

Keywords

  • Dodecapeptide
  • Fibrinogen
  • GPIIb/IIIa
  • Hemostasis
  • Human
  • Rat

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets. / Tokutomi, Koji; Tagawa, Toshiaki; Korenaga, Maki; Chiba, Masatoshi; Asai, Tomohiro; Watanabe, Naohide; Takeoka, Shinji; Handa, Makoto; Ikeda, Yasuo; Oku, Naoto.

In: International Journal of Pharmaceutics, Vol. 438, No. 1-2, 15.11.2012, p. 296-301.

Research output: Contribution to journalArticle

Tokutomi, K, Tagawa, T, Korenaga, M, Chiba, M, Asai, T, Watanabe, N, Takeoka, S, Handa, M, Ikeda, Y & Oku, N 2012, 'Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets', International Journal of Pharmaceutics, vol. 438, no. 1-2, pp. 296-301. https://doi.org/10.1016/j.ijpharm.2012.09.016
Tokutomi, Koji ; Tagawa, Toshiaki ; Korenaga, Maki ; Chiba, Masatoshi ; Asai, Tomohiro ; Watanabe, Naohide ; Takeoka, Shinji ; Handa, Makoto ; Ikeda, Yasuo ; Oku, Naoto. / Ability of fibrinogen γ-derived dodecapeptides with different sequences to bind to rat platelets. In: International Journal of Pharmaceutics. 2012 ; Vol. 438, No. 1-2. pp. 296-301.
@article{a2ec9fa95b234371bcddb82a66daf1a6,
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 (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.",
keywords = "Dodecapeptide, Fibrinogen, GPIIb/IIIa, Hemostasis, Human, Rat",
author = "Koji Tokutomi and Toshiaki Tagawa and Maki Korenaga and Masatoshi Chiba and Tomohiro Asai and Naohide Watanabe and Shinji Takeoka and Makoto Handa and Yasuo Ikeda and Naoto Oku",
year = "2012",
month = "11",
day = "15",
doi = "10.1016/j.ijpharm.2012.09.016",
language = "English",
volume = "438",
pages = "296--301",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

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

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

VL - 438

SP - 296

EP - 301

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -