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The platelet glycoprotein Ib(alpha) (GPIb(alpha)) receptor contains a high-affinity binding site for thrombin that, when occupied, augments platelet activation and aggregation in part via the 7-transmembrane domain receptor (7-TMDR). We have constructed a series of peptides derived from GPIb(alpha) that encompass the amino acid sequence F216-T240. We have studied the effect(s) of these peptides on platelet aggregation induced by thrombin or by the 7-TMDR peptide SFLLRN. Twenty-four peptides were synthesized from the peptide sequence F216-T240. Several of the peptides derived from the sequence W219-V227 of GPIb(alpha) inhibited platelet aggregation, which was primarily dependent on the presence of the amino acid sequence A224-N226 (AEN). These data suggest that a region within the GPIb(alpha) chain modulates the platelet aggregation induced by alpha-thrombin. These GPIb(alpha) peptides did not interfere with platelet aggregation induced by other agonists--for example, collagen, ristocetin, calcium ionophore, or botrocetin--which indicates that these GPIb(alpha) peptide-platelet interaction(s) are specific. Our studies provide another potential mechanism for modulating platelet activation and aggregation via synthetic and natural peptides.
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
June 2001,
The Journal of biological chemistry,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
December 1991,
The Journal of biological chemistry,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
November 2003,
Trends in molecular medicine,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
April 1997,
American journal of hematology,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
September 1993,
British journal of haematology,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
July 2000,
The Journal of biological chemistry,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
April 2003,
Journal of thrombosis and haemostasis : JTH,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
January 1992,
Seminars in thrombosis and hemostasis,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
January 1996,
Seminars in thrombosis and hemostasis,
L P McKeown, and
S B Williams, and
K E Hansmann, and
H Krutzsch, and
H R Gralnick
March 1994,
The Journal of biological chemistry,
