Glycoprotein Ib alpha peptides inhibit thrombin and SFLLRN-induced platelet aggregation.
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.
Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
L P
LP
McKeown
S B
SB
Williams
K E
KE
Hansmann
H
H
Krutzsch
H R
HR
Gralnick
D000595:Amino Acid Sequence; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D018179:Receptors, Thrombin / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D009842:Oligopeptides; D010446:Peptide Fragments; D019038:Platelet Glycoprotein GPIb-IX Complex; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D013917:Thrombin