PMID- 1888330
OWN - NLM
STAT- MEDLINE
DCOM- 19911004
LR  - 20191210
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 42
IP  - 6
DP  - 1991 Aug 22
TI  - Halysin, an antiplatelet Arg-Gly-Asp-containing snake venom peptide, as 
      fibrinogen receptor antagonist.
PG  - 1209-19
AB  - By means of Sephadex G-75 and CM-Sephadex C-50 column chromatography and 
      reverse-phase HPLC, a low molecular weight (Mr = 7500), cysteine-rich peptide, 
      halysin, was purified from Agkistrodon halys (mamushi) snake venom. Halysin is a 
      potent platelet aggregation inhibitor that concentration-dependently inhibited 
      human platelet aggregation stimulated by ADP, thrombin and collagen (IC50 = 0.16 
      to 0.36 microM) without affecting platelet secretion. It was active in inhibiting 
      platelet aggregation of platelet-rich plasma and whole blood. Halysin had no 
      effect on thromboxane B2 formation of platelets or intracellular Ca2+ 
      mobilization of Quin 2-AM loaded platelets stimulated by thrombin. It inhibited 
      the fibrinogen-induced aggregation of elastase-treated platelets. Halysin 
      concentration-dependently inhibited the 125I-fibrinogen binding to ADP-stimulated 
      platelets in a competitive manner (IC50 = 0.16 microM). 125I-Halysin bound to 
      resting platelets (Kd = 1.6 x 10(-7) M) and to ADP-stimulated platelets (Kd = 3.4 
      x 10(-8) M) in a saturable manner. EDTA, the Arg-Gly-Asp (RGD)-containing snake 
      venom peptides trigamin and rhodostomin, Arg-Gly-Asp-Ser (RGDS), and 
      Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val blocked both 
      125I-fibrinogen binding and 125I-halysin binding to ADP-stimulated platelets. The 
      monoclonal antibody, 7E3, raised against glycoprotein IIb-IIIa complex blocked 
      both 125I-fibrinogen and 125I-halysin binding, whereas 10E5 had no significant 
      effect on halysin binding to ADP-stimulated platelets, indicating that 7E3 and 
      halysin bind to an epitope which is different from that of 10E5. RGDS 
      concentration-dependently inhibited 125I-halysin binding in a competitive manner. 
      We determined the primary structure of halysin which is a single peptide chain of 
      71 amino acid residues. An RGD sequence appeared in the carboxy-terminal domain 
      of halysin. Halysin showed about an 85% identical sequence with trigamin which is 
      a specific antagonist of fibrinogen receptor associated with glycoprotein 
      IIb-IIIa complex. In conclusion, halysin inhibited platelet aggregation by 
      interfering with fibrinogen binding to the fibrinogen receptor of the activated 
      platelets. The RGD sequence of halysin plays an important role in the expression 
      of its biological activity.
FAU - Huang, T F
AU  - Huang TF
AD  - College of Medicine, National Taiwan University, Taipai, Republic of China.
FAU - Liu, C Z
AU  - Liu CZ
FAU - Ouyang, C H
AU  - Ouyang CH
FAU - Teng, C M
AU  - Teng CM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Aminoquinolines)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Crotalid Venoms)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Peptides)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 111019-84-2 (trigramin)
RN  - 137544-79-7 (halysin)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 83104-85-2 (Quin2-acetoxymethyl ester)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9001-32-5 (Fibrinogen)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Diphosphate/pharmacology
MH  - Adenosine Triphosphate/metabolism
MH  - Amino Acid Sequence
MH  - Aminoquinolines/pharmacology
MH  - Antibodies, Monoclonal
MH  - Binding, Competitive
MH  - Blood Platelets/drug effects/physiology
MH  - Calcium/metabolism
MH  - Crotalid Venoms/*analysis/*isolation & purification/metabolism
MH  - Fibrinogen/antagonists & inhibitors/metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Pancreatic Elastase/pharmacology
MH  - Peptides/analysis
MH  - Platelet Aggregation Inhibitors/*isolation & purification
MH  - Platelet Membrane Glycoproteins/*antagonists & inhibitors
MH  - Thromboxane B2/biosynthesis
EDAT- 1991/08/22 00:00
MHDA- 1991/08/22 00:01
CRDT- 1991/08/22 00:00
PHST- 1991/08/22 00:00 [pubmed]
PHST- 1991/08/22 00:01 [medline]
PHST- 1991/08/22 00:00 [entrez]
AID - 0006-2952(91)90256-5 [pii]
AID - 10.1016/0006-2952(91)90256-5 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1991 Aug 22;42(6):1209-19. doi: 10.1016/0006-2952(91)90256-5.